Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Thromboangiitis obliterans. Core disease mechanisms, molecular and cellula...

This report is retrieval-only and is generated directly from Asta results.

• Papers retrieved: 19
• Snippets retrieved: 20

Relevant Papers

[1] CASE REPORT OF BUERGER’S DISEASE WITH GANGRENOUS GALL BLADDER AND SMALL GUT

• Authors: Manju Singh, Gambheer Singh, A. Agrawal, Sandeep Chandrakar
• Year: 2014
• Venue: Journal of Evolution of medical and Dental Sciences
• URL: https://www.semanticscholar.org/paper/dce102d9fbe95a0c054b4b857ce425670d54827a
• DOI: 10.14260/jemds/2014/3679
• Summary: A case of intestinal obstruction in a 50 year male patient of Buerger’s disease which contained gangrenous gall bladder is presented and an exploratory laparotomy was done.
• Evidence snippets:
• Snippet 1 (score: 0.622) > Exposure to tobacco is central to the initiation, maintenance, and progression of Thromboangiitis Obliterans. Although smoking tobacco is by far the most common risk factor, it may also develop as a result of chewing tobacco or marijuana use. Nearly two thirds of patients with Thromboangiitis Obliterans have severe periodontal disease and chronic anaerobic periodontal infection may represent an additional risk factor for the development of the disease. Polymerase chain reaction analysis demonstrated DNA fragments from anaerobic bacteria in both arterial lesions and oral cavities of patients with Thromboangiitis Obliterans but not in arterial samples from healthy control subjects. > PATHOPHYSIOLOGY: Thromboangiitis Obliterans is a vasculitis characterized by a highly cellular inflammatory thrombus with relative sparing of the vessel wall. Although acute-phase reactants such as erythrocyte sedimentation rate, C-reactive protein and commonly measured autoantibodies are typically normal, abnormalities in immune reactivity are believed to drive the inflammatory process. Patients with Thromboangiitis Obliterans have been shown to have increased cellular immunity to types I and III collagen compared with those who have atherosclerosis. 3 In addition, high titers of ant endothelial cell antibodies have been detected in patients with this disorder. 4 rothrombotic and hemorheologic factors may also play a role in the pathophysiology of Thromboangiitis Obliterans. The prothrombin gene mutation 20210 5 and the presence of anticardiolipin antibodies 6 are associated with an increased risk of the disease. Thromboangiitis Obliterans patients with high anti cardiolipin antibody titers tend to have a younger age of onset and an increased rate of major amputation compared with patients who do not have detectable antibodies. 6 Hemorheologic parameters such as hematocrit, red blood cell rigidity, and blood viscosity are increased in patients with Thromboangiitis Obliterans compared with those with atherosclerosis. 7 hromboangiitis Obliterans involves 3 phases: acute, sub-acute, and chronic.

[2] The Imbalance among Oxidative Biomarkers and Antioxidant Defense Systems in Thromboangiitis Obliterans (Winiwarter-Buerger Disease)

• Authors: H. Sharebiani, B. Fazeli, R. Maniscalco, D. Ligi, F. Mannello
• Year: 2020
• Venue: Journal of Clinical Medicine
• URL: https://www.semanticscholar.org/paper/0fc63f0246d05338cba04487c7d5903236e7fcba
• DOI: 10.3390/jcm9041036
• PMID: 32272606
• PMCID: 7231233
• Citations: 26
• Influential citations: 1
• Summary: Considerably high levels of oxidative stress were detected in WBD patients, which were greater than the antioxidant capacity, representing a promising tool to discern possible different clinical risks of this poorly understood peripheral occlusive disease.
• Evidence snippets:
• Snippet 1 (score: 0.552) > Since the milestone landmark articles [1,2], thromboangiitis obliterans or Winiwarter-Buerger disease (WBD) has been defined as an inflammatory, thrombotic, occlusive, peripheral vascular disease, which usually occurs in young male smokers. The occlusion of small-and medium-sized vessels (arteries and veins of both upper and lower extremities) may lead to tissue or limb loss [3]. Although the clinic-pathological hallmarks, and some molecular mechanisms have been studied, the etiology, pathophysiology, and optimal therapy remain not yet fully defined or understood [4]. Although a significant relationship between smoking (both tobacco and cannabis products) and progression of WBD has been identified [5], smoking per se cannot explain the prevalence and distribution of this harmful vascular disease [6]. Despite efforts in previous years and advances in medical therapy [4,7,8], WBD patients may actually benefit only by blocking smoking habits (abstinence of all tobacco/cannabis product use) and through targeted endovascular therapy, effective for preserving limb loss/amputation, and useful for accelerating the healing process in Buerger's ischemic ulcers [9]. > Among the immunologic and inflammatory biomolecular hypotheses for the WBD disease, some biomarkers and biochemical mechanisms have been identified.
• Snippet 2 (score: 0.534) > Winiwarter-Buerger disease (WBD) or thromboangiitis obliterans has been clearly defined as a serious medical and social problem, characterized as a nonatherosclerotic, inflammatory vasculitis strongly associated with smoking and affecting vessels of both upper and lower extremities [4,47]. > WBD is characterized as a nonatherosclerotic thrombotic occlusive peripheral vascular disease, affecting arteries and veins with the presence of highly inflammatory thrombus [47][48][49]. Although strongly associated to the use of tobacco and cannabis products use, per se, are not justifying the well described oxidative stress responsible for the progression and worsening of this disease, sadly suggesting that little progress has been made in the understanding of its pathophysiology and treatment [4,8,50]. > Although several studies have focused on discern the molecular mechanisms involved in the etiopathogenesis and pathophysiology pathways (as reviewed in [51,52]), and according to some studies performed to evaluate different oxidative and antioxidant pathways in Winiwarter-Buerger disease [30,31,53,54], to our knowledge, the present study is the first report demonstrating a possible link between SOD and MDA down-regulations, related also to a significant increase of CoQ10 levels in WBD, with respect to healthy smokers. > Despite the studies on pathophysiology (reviewed in [29,51], actually, the detailed etiopathogenesis and molecular mechanisms are still unknown. Among the possible biomolecular hypotheses [10,12,14,18,[20][21][22][23]27,50,[54][55][56], oxidative stress has been crucially indicated as an important factor for both the initiation and progression of WBD [30,31,51,54]. > According to our previous results [31] and literature data [30] (reviewed in [51]), in WBD there is an evident and significant impairment of the balance between oxidative stress and the anti-oxidant capacity.

[3] Top 100 cited articles in the thromboangiitis obliterans: a bibliometric analysis and visualized study

• Authors: Zhenxing Liu, Weiwei Ning, Jinlong Liang, Tao Zhang, Qingxu Yang et al.
• Year: 2023
• Venue: European Journal of Medical Research
• URL: https://www.semanticscholar.org/paper/1f5a0a98d6c55e9a7427d0f6875f80e35a401174
• DOI: 10.1186/s40001-023-01540-6
• PMID: 38042838
• PMCID: 10693135
• Citations: 6
• Summary: The highly cited contributors in the field of TAO research were identified and treatment and pathophysiology including stem cell therapy, progenitor therapy, genetics, autoimmunity, and inflammation are the hotspots of TAO.
• Evidence snippets:
• Snippet 1 (score: 0.540) > The places that researchers are looking at represent the hotspots in a certain period, however, it cannot always reflect the right places to look, for example, the illustration of pathology and surgical treatment of TAO. Thromboangiitis obliterans is now generally accepted as an autoimmune disease; besides, clinical findings revealed that thromboangiitis obliterans patients tend to familial aggregation and genetic predisposition [8]. The novel findings in the mechanism of diseases incubated the auto-immunological therapies, especially autologous cell therapy [4]. The knowledge gaps and novel ideas for investigation can be revealed by the analysis of hotspots of these top-cited articles. > We constructed two diagrams to visually represent the research domains of original articles and reviews. These diagrams were created based on their categorizations, which encompassed epidemiology, etiology, pathophysiology, diagnosis, treatment, and prognosis (Additional file 1: Tables S3 and S4). In the case of pathophysiology, we further segmented it into distinct sections, delineating various aspects such as the immune system, genetics, endothelial dysfunction, autoimmunity, inflammation, coagulation and thrombosis, genetics, and epigenetics. Likewise, the treatment category underwent a refined classification, differentiating between medicine, endovascular surgery, cellular therapy, and innovative therapeutic approaches. > Within the realm of original articles, encompassing clinical trials, case series, and case-control studies, our investigation revealed that treatment and pathophysiology were the most frequently addressed aspects. Interestingly, manifestations, etiology, diagnosis, prognosis, and epidemiology garnered relatively less attention. This suggests that original research predominantly centered around the treatment of TAO, often sidelining the assessment of prognosis. In the case of review articles, a different pattern emerged, with an emphasis on summarizing treatment and diagnosis, closely followed by discussions on pathogenesis. In contrast, manifestation, prognosis, and epidemiology received comparatively less coverage. In summation, reviews predominantly concentrated on diagnosis, and treatment was a recurring focal point in the top 100 cited articles.

[4] Thromboangiitis Obliterans (Buerger's Disease)

• Authors: Nicholas R. Sinclair, D. Laub
• Year: 2015
• Venue: Eplasty
• URL: https://www.semanticscholar.org/paper/7ee7114ffc83db093d06a39756d47aa83b5f91db
• PMID: 25987945
• PMCID: 4404841
• Summary: Figure 1. Black and gangrenous eschar tissue in the right third digit previously amputated to the middle phalanx with distal gangrene and erythema around the right middle metacarpophalangeal joint.
• Evidence snippets:
• Snippet 1 (score: 0.540) > showing the acute-phase inflammatory cell thrombus, this is not always possible and usually not necessary. In most cases, thromboangiitis obliterans is diagnosed clinically. Common clinical diagnostic criteria include age less than 45 years, history of tobacco use, vascular testing demonstrating distal extremity ischemia, and arteriographic evidence consistent with thromboangiitis obliterans (lack of atherosclerosis, segmental occlusion, collateralization around occlusions, and lack of proximal source of thromboembolism). 5 Serological markers of autoimmune disease and a hypercoagulability screen should be performed to rule out alternative diagnoses. As mentioned earlier, prothrombin gene mutation 20210 and anticardiolipin antibodies have been associated with thromboangiitis obliterans and do not establish the diagnosis. > The definitive treatment of thromboangiitis obliterans is tobacco cessation. Pharmacotherapy (bupropion or varenicline) and group therapy should be offered. Nicotine replacement should be avoided, as this may continue the progression of the disease. 5 While thromboangiitis obliterans will remit with tobacco cessation, irreversible ischemic changes of tissue loss and gangrene will not. These complications are usually treated with amputation of the affected area (Fig 3). Iloprost, a prostaglandin agonist, has been shown to be more effective than lumbar sympathectomy in managing pain and healing ulcers, especially before tobacco use has been fully stopped. 6 Recent research in therapeutic angiogenesis, including intramuscularly administered VEGF (vascular endothelial growth factor) 7 and autologous bone marrow mononuclear cell implantation, 8 has shown promise but are not yet utilized clinically. > Thromboangiitis obliterans should be suspected in any patient using tobacco products who presents with new-onset superficial thrombophlebitis or distal extremity pain. Initial evaluation should consist of a thorough history and physical examination. Laboratory testing should be done to rule out diabetes, autoimmune disease, or hyperco

[5] Endarteritis obliterans in the pathogenesis of Buerger's disease from the pathological and immunohistochemical points of view.

• Authors: Masayoshi Kobayashi, M. Sugimoto, K. Komori
• Year: 2014
• Venue: Circulation journal : official journal of the Japanese Circulation Society
• URL: https://www.semanticscholar.org/paper/ae9917f03191a33ac6124c79ecc26ebc09c734a8
• DOI: 10.1253/CIRCJ.CJ-14-0656
• PMID: 25298073
• Citations: 23
• Influential citations: 1
• Summary: The possibility that the pathogenesis of Buerger's disease is a type of endarteritis obliterans, deeply connected to the Notch pathway, distinct from arteriosclerosis obliterans and other vasculitides is discussed.
• Evidence snippets:
• Snippet 1 (score: 0.539) > Buerger's disease (thromboangiitis obliterans) is considered to be a nonatherosclerotic, inflammatory, and vaso-occlusive disease, although the details of the mechanisms of pathogenesis remain unknown. The occurrence of the disease is strongly related to tobacco abuse and its progression is closely linked to continued smoking. The purpose of this review article is to demonstrate the pathological characteristics of arteries affected with Buerger's disease from a possible immunoreactive point of view. In addition, we present the mechanisms for preserving the architecture of the arterial wall in affected vasculatures. Thereafter, we discuss the possibility that the pathogenesis of Buerger's disease is a type of endarteritis obliterans, deeply connected to the Notch pathway, distinct from arteriosclerosis obliterans and other vasculitides.

[6] Molecular mechanisms regulating immune responses in thromboangiitis obliterans: A comprehensive review

• Authors: A. Shapouri-Moghaddam, Mohammad-Hadi Saeed Modaghegh, H. Rahimi, Seyyed-Morteza Ehteshamfar, J. Tavakol Afshari
• Year: 2019
• Venue: Iranian Journal of Basic Medical Sciences
• URL: https://www.semanticscholar.org/paper/6547489b6a8b92d010aa7829c98f3943ab6f601b
• DOI: 10.22038/ijbms.2019.31119.7513
• PMID: 31156780
• PMCID: 6528722
• Citations: 21
• Summary: The more current knowledge on the regulatory molecules involved in TAO from an immunoreactive perspective is collated to improve understanding of the crosstalk between angiogenesis and the immune system, as well as the potential of new co-targeting strategies applying both immunotherapy and angiogenic therapy.
• Evidence snippets:
• Snippet 1 (score: 0.524) > Thromboangiitis obliterans (TAO) is described as a non-atherosclerotic segmental inflammatory and occlusive vascular disease which mainly involves the small-and medium-sized arteries, veins, and nerves of the upper and lower extremities (1). Despite intriguing advances in the clinical understanding of TAO (2)(3)(4)(5), there is still a lack of detailed reports on the molecular evidence underlying immune responses in the disease. Hitherto, four factors have been identified to affect the pathogenesis of Buerger's disease: variant of atherosclerosis; immunologic arteritis; odontal bacterial thrombosis; hyperhomocysteinemia. Thus, Buerger's disease is representative of immunemediated arteritis based on the immunocytochemical evidence, characterized by the accumulation of immunoglobulins and complement factors in the vessel wall (6). Moreover, some have reported an elevation of cellular immunity to type I and type III collagens (7). The presence of antiendothelial antibodies has been determined, which is indicative of the immune response towards the endothelium (8). Such findings have drawn attentions towards the role of the immune system in the development of TAO. This review aimed at elucidating the molecular mechanisms implicated in the dysregulation of the immune response during the disease process.

[7] Influence of cilostazol on thromboangiitis obliterans in rats and the mechanism involved

• Authors: Weiliang Zhu, Jian-Li Ying
• Year: 2022
• Venue: Tropical Journal of Pharmaceutical Research
• URL: https://www.semanticscholar.org/paper/6280e6b6e5cc56dcecb4819b124206238cbf5e15
• DOI: 10.4314/tjpr.v21i7.19
• Summary: Cilostazol alleviates sodium laurate-induced TAO lesions in rats via HIF-1α/VEGF pathway through the hypoxia-inducible factor/vascular endothelial growth factor pathway may provide new insights for the treatment of TAO.
• Evidence snippets:
• Snippet 1 (score: 0.492) > Thromboangiitis obliterans (TAO) is a common peripheral vascular disease of unknown cause and pathogenesis, and it is characterized by a high risk of amputation as well as a high incidence rate. There is still a scarcity of definite therapies so far [1]. Thromboangiitis obliterans is accompanied by recurrent superficial thrombophlebitis and upper limb involvement, and while smoking cessation can hinder the progression of this disease, it is unable to prevent it from worsening. Both the immune system and inflammations play a key role in the pathogenesis of TAO [2,3]. Although the reactants at an acute stage generally have normal erythrocyte sedimentation rate and Creactive protein, as well as the usually-measured autoantibodies, the abnormality of immunoreactivity is considered as a driver for the inflammatory processes. Compared with those with atherosclerosis, TAO patients have enhanced cellular immunity to type I and II collagen [4]. Moreover, high-titer anti-endothelial cell antibodies are seen in these patients [5]. > In multiple randomized clinical trials, Cilostazol has proven to be able to reduce the incidence of coronary in-stent restenosis, and its pharmacological actions include vasodilation, inhibiting of thrombosis, increasing the blood flow of limbs, improving serum lipid, decreasing triglyceride, raising high-density lipoprotein cholesterol and suppressing the growth of vascular smooth muscle cells [6]. Cilostazol is used to treat patients with intermittent claudication and peripheral vascular disease worldwide, and while it is recommended for the prevention of secondary stroke in Asia [7], its effect on TAO has yet to be fully understood. > The present study explored the therapeutic effect of cilostazol on the recovery of affected limbs and the vascular lesions in the rat models of TAO, and elucidated on its mechanism of action in the occurrence and development of TAO.

[8] Macrophage Paired Immunoglobulin-Like Receptor B Deficiency Promotes Peripheral Atherosclerosis in Apolipoprotein E–Deficient Mice

• Authors: Wenhua Su, Liwen Liang, Liang Zhou, Yu Cao, Xiuli Zhou et al.
• Year: 2022
• Venue: Frontiers in Cell and Developmental Biology
• URL: https://www.semanticscholar.org/paper/369e03a3bc199af07a690f7aee3155c98a720f0e
• DOI: 10.3389/fcell.2021.783954
• PMID: 35321392
• PMCID: 8936951
• Citations: 2
• Summary: A myeloid-specific PirB-knockout Apoe −/− murine model of PAD (PirB MΦKO) is created to analyze femoral atherosclerotic burden, plaque features of vulnerability, and monocyte recruitment to femoral atheism lesions to explore the role of the murine LILRB2 homologue PirB in vivo.
• Evidence snippets:
• Snippet 1 (score: 0.471) > The narrowing or blockage of arteries that supply blood to the lower limbs is known as peripheral atherosclerotic disease (PAD). The principal cause of PAD is the atherosclerotic occlusion of arteries supplying the affected limbs. Although the disease is mostly asymptomatic, a commonplace clinical presentation is intermittent claudication (i.e., pain on walking). More severe clinical manifestations include critical limb ischemia (CLI), which presents as pain even during rest as well as tissue loss due to ulceration or gangrene (Morley et al., 2018). PAD is estimated to affect about 13% in adults of the Western population aged 50 or above (Morley et al., 2018). Mortality due to cardiovascular disease is seen in 10-15% of patients with intermittent claudication within 5 years of diagnosis (Norgren et al., 2007). Based on this evidence, it is important to identify the pathophysiological mechanism(s) underlying PAD progression, which can provide guidance towards more effective management of PAD patients. > However, the molecular pathophysiology underlying PAD is complicated, as there are a number of pathways, proteins, and cell types involved in PAD progression (Scholz et al., 2002;Coats and Wadsworth, 2005;Kuang et al., 2008). The primary cells implicated in the development of PAD include macrophages, vascular endothelial cells (ECs), resident stem cells, platelets, vascular smooth muscle cells (SMCs), fibroblasts, and pericytes (Scholz et al., 2002;Coats and Wadsworth, 2005;Kuang et al., 2008). In an otherwise healthy individual, tissue damage due to progressive limb ischemia progresses along a continuum. Initially, the body attempts to homeostatically restore blood supply to the affected limb(s) by angiogenic and arteriogenic pathways. To further resolve limb ischemia and tissue damage, inflammatory, vascular remodeling, and apoptotic pathways are activated. However, in patients diagnosed with CLI, such compensatory mechanisms are inefficient to restore sufficient blood flow.

[9] Knowledge Mapping of Global Status and Trends for Thromboangiitis Obliterans: A Bibliometrics and Visual Analysis

• Authors: Ze-Bin Liu, Chenhan Zhou, Hongbin Guo, Min Wang, Jieyun Liang et al.
• Year: 2023
• Venue: Journal of Pain Research
• URL: https://www.semanticscholar.org/paper/09a85b900717abb32204e22add8ed7bd31bb0dec
• DOI: 10.2147/JPR.S437521
• PMID: 38054111
• PMCID: 10695024
• Citations: 5
• Summary: The number of TAO publications has fluctuated over the past 20 years, but it has generally shown a steady upward trend and some keywords such as trail, therapy, outcome, management, stem cells, angioplasty, and activation will become a hot spot in the future.
• Evidence snippets:
• Snippet 1 (score: 0.464) > The top 10 most-cited articles are shown in Table 5. The first one refers to Olin, J.W., 21 they summarized the latest progress of TAO from four aspects: cause and pathogenesis, pathological findings, clinical features, treatment. > The second one is written by Flammer, J. et al. 23 They discussed the role of vasospasm in the pathogenesis of the disease. The third one refers to Matoba, S. et al. They conducted a randomized controlled trial (Therapeutic Angiogenesis by Cell Transplantation) to testify the feasibility of bone marrow mononuclear cells injection in patients with critical limb ischemia. > Keywords stand for the essence and core of a paper, which reflect the research hotspots in the field. The top 5 keywords ranked in this study and their frequencies are thromboangiitis obliterans (177), thromboangiitis-obliterans (151), buerger's disease (150), buergers-disease (115), critical limb ischemia (60). By clustering the keywords with frequency more than or equal to 10, a total of 71 qualified keywords were obtained and grouped into four clusters (Figure 8A). Green clusters represent "Cell therapy study", mainly about endothelial progenitor cell; blue clusters represent "Mechanism study", mainly about inflammation; red clusters represent "Etiology study", mainly about smoking; yellow clusters represent studies on "Clinical therapy study", mainly about sympathectomy. Figure 8B shows the map of co-occurring keywords over time. In this figure, different colors indicate the relevant year of publication. Yellow keywords came later than blue keywords. In addition, a burst keyword means the word that occur frequently within a specific time period. It shows the evolution of research hotspots over time, which indicates the research trends recently and foreshadow future trends (Figure 9). The burst keyword with highest strength is endothelial progenitor cells. However, trial, therapy, outcome, and management have received much attention in recent years.

[10] An Unusual Case of Thromboangiitis Obliterans With Concurrent Deep Vein Thrombosis and Pulmonary Embolism

• Authors: Z. Vaezi, Donica L Baker
• Year: 2025
• Venue: Cureus
• URL: https://www.semanticscholar.org/paper/415a38119f254f686ee564df8f060e12542f1596
• DOI: 10.7759/cureus.96506
• PMID: 41384188
• PMCID: 12695112
• Summary: Clinicians should maintain suspicion for PE in TAO patients with unexplained respiratory symptoms and emphasize tobacco cessation as essential for preventing recurrence and progression, especially in the setting of systemic inflammation.
• Evidence snippets:
• Snippet 1 (score: 0.448) > Buerger's disease, also known as thromboangiitis obliterans (TAO), is a rare, segmental, inflammatory, and thrombotic vasculitis that primarily affects small-and medium-sized arteries and veins, typically in the distal extremities. First described by Leo Buerger in 1908, the disease is most commonly seen in young adult males with a strong history of tobacco use [1]. However, more recent case series and reports suggest that the clinical spectrum may be broader, occasionally affecting women and patients with comorbidities such as diabetes mellitus [2,3]. The pathogenesis of TAO is not entirely understood but appears to involve an interplay between genetic susceptibility, tobacco exposure, immune-mediated endothelial injury, and coagulation abnormalities. Histologically, it is characterized by a highly cellular thrombus with relative sparing of the internal elastic lamina and a panvasculitis picture involving both arteries and veins [2]. > Several hypotheses have been proposed to explain the underlying mechanisms driving TAO. Serotonin dysregulation has been implicated in promoting vasospasm and thrombus formation in TAO patients [4]. Furthermore, autoimmune processes appear to play a significant role, particularly in individuals with specific human leukocyte antigen (HLA) phenotypes, where tobacco antigens may act as immunologic triggers [5]. Neurovascular dysfunction, as explored in treatments involving spinal cord stimulation, also supports the notion that vasomotor instability may contribute to ischemic episodes in TAO [5]. The disease classically affects the lower limbs but can occasionally involve visceral arteries, with rare but severe presentations such as mesenteric ischemia and small bowel infarction [6]. A recent comprehensive review of 91 patients from Iran further illustrated the diverse presentation of TAO, including both arterial and venous thromboses [7]. > Although TAO is primarily regarded as a peripheral vascular disorder, emerging literature hints at possible systemic vascular involvement, raising the question of whether central thromboembolic complications, such as pulmonary embolism (PE), might occur in some patients.

[11] Circulating Angiogenic Factors in Patients with Thromboangiitis Obliterans

• Authors: B. Hewing, V. Stangl, K. Stangl, K. Enke-Melzer, G. Baumann et al.
• Year: 2012
• Venue: PLoS ONE
• URL: https://www.semanticscholar.org/paper/d03a0eec1dca19c43f7a6cbcee1461f55606dc44
• DOI: 10.1371/journal.pone.0034717
• PMID: 22506045
• PMCID: 3323572
• Citations: 18
• Influential citations: 2
• Summary: Levels of circulating progenitor cells were altered inTAO patients compared to healthy nonsmokers and smokers, and serum of TAO patients exhibited an antiangiogenic activity on endothelial cells, which may contribute to vascular pathology in this patient population.
• Evidence snippets:
• Snippet 1 (score: 0.447) > Thromboangiitis obliterans (TAO, also known as Buerger's disease) is a non-atherosclerotic segmental inflammatory vascular disease that primarily affects small and medium sized arteries and veins of the extremities. TAO is observed worldwide with the highest prevalence in the Middle and Far East. Although the disease was first described in 1879 the etiology and pathogenesis of TAO still remains unknown. However, tobacco consumption plays a key role in the initiation and persistence of the disease. TAO typically affects young, male smokers, but the incidence in women is increasing due to tobacco consumption [1,2]. > Generally, intermittent claudication is the first clinical symptom that may progress to critical ischemia with rest pain, digital gangrene and ulcers, finally resulting in amputation of the affected extremity. The prognosis of TAO patients is closely related to smoking. Therefore complete smoking cessation is the most important therapy for TAO and necessary to prevent disease progression and to avoid amputation. Beside the local care of ischemic complications therapeutic options are limited to prostaglandins, anticoagulants, anti-inflammatory agents, immunoad-sorption and sympathectomy. In most cases surgical revascularization is not feasible due to the distal location and diffuse vascular occlusions in TAO [2][3][4]. > The ischemic condition subsequent to occlusion of the vascular lumen promotes angiogenesis and arteriogenesis leading to the development of collaterals in the affected extremities of TAO patients. A growing number of studies focus on therapeutic angiogenesis as a treatment strategy in patients with coronary artery disease, peripheral arterial disease and also in TAO [5]. In a small clinical trial with TAO patients the intramuscular administration of recombinant vascular endothelial growth factor (VEGF) resulted in the healing of ischemic ulcers and relief of rest pain [6]. Increasing evidence suggests that an alteration in stem cell function plays a role in the pathogenesis of vascular diseases [7].

[12] Administration of Adult Human Bone Marrow‐Derived, Cultured, Pooled, Allogeneic Mesenchymal Stromal Cells in Critical Limb Ischemia Due to Buerger’s Disease: Phase II Study Report Suggests Clinical Efficacy

• Authors: P. Gupta, M. Krishna, Anoop Chullikana, S. Desai, R. Murugesan et al.
• Year: 2016
• Venue: Stem Cells Translational Medicine
• URL: https://www.semanticscholar.org/paper/7c86c82aa9fe975db79de27478cf12193da95814
• DOI: 10.5966/sctm.2016-0237
• PMID: 28297569
• PMCID: 5442769
• Citations: 58
• Influential citations: 1
• Summary: Administration of BMMSC at a dose of 2 million cells/kg showed clinical benefit and may be the best regimen in patients with CLI due to Buerger’s disease, however, further randomized controlled trials are required to confirm the most appropriate dose.
• Evidence snippets:
• Snippet 1 (score: 0.439) > Thromboangiitis obliterans, also known as Buerger's disease, is a nonatherosclerotic, segmental inflammatory disease that most commonly affects the small and medium-sized arteries and veins in the upper and lower extremities [1]. The disease progresses to critical limb ischemia (CLI), manifested clinically as rest pain, incurable ulceration, gangrene, and toe or limb loss. Because the possibility of vascular bypass is usually small as a result of diffuse segmental involvement and the distal nature of the disease [2], the consequence of the disease in the more advanced stage may be limb amputation, especially of the lower extremities [3]. Consequently, there is increasing ongoing research on the use of additional interventions for therapeutic angiogenesis, such as cell-based therapy [4][5][6][7][8][9], gene therapy [10,11] and immunoabsorption therapy [12] in these "no option" patients with CLI. > Our previous report [13] showed that use of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (BMMSCs; Stempeucel, Stempeutics Research, Bangalore, India, http://www.stempeutics.com ) was safe when injected via the i.m. route at a dose of 2 million cells/kg body weight in patients with CLI. The probable mechanism of action of Stempeucel is likely due to a combinatorial effect of antiinflammatory and proangiogenic activity governed by paracrine function or by directly producing the cytokines and growth factors at the site of inflammation and ulcer location. > Most Buerger's disease patients in India are relatively young male smokers in families belonging to low socioeconomic strata [14]; this causes economic morbidity in the family and society alike. Studies have shown that approximately 0.4 million people in India are affected by CLI due to Buerger's disease [15], indicating the gravity of the disease in this country. Given the limitation of the current therapies and high rate of amputations

[13] Potential molecular mechanisms of postoperative restenosis in lower extremity Atherosclerotic occlusive disease

• Authors: Zilin Lu, Xianfei Liu, Peiqi Li
• Year: 2024
• Venue: International Conference on Biomedical and Intelligent Systems
• URL: https://www.semanticscholar.org/paper/2660570fd6b66ac7c652b5a9bc98d9cd802d8b6e
• DOI: 10.1117/12.3036630
• Summary: It is concluded that matrix metalloproteinase 9 (MMP9) may play a key role in the onset and progression of ASO in lower extremity artery by controlling smooth muscle cell phenotypic shift.
• Evidence snippets:
• Snippet 1 (score: 0.436) > Arteriosclerosis obliterans (ASO) is a common peripheral arterial disease, characterized by atherosclerotic plaque formation that leads to narrowing or occlusion of the peripheral artery, resulting avascular necrosis of the limbs [1]. According to recent statistics, more than 200 million people worldwide have a lower peripheral arterial disease (toe brachial index less than 0.7), with an increased incidence accompanied by age and risk factors [2]. The disease is often severe by the time with insufferable symptoms, such as intermittent claudication and resting pain, while there is no significant clinical manifestations at the early stages of ASO. Endoluminal therapy has been effective in treating the disease, but the incidence of restenosis remains high at 40% [3]. For those patients who are experiencing postoperative restenosis may have been threatened by a much higher risk of amputation and death. Although it is clear that the prevention of stent restenosis has a significant impact on patients [4][5][6], our current understanding of the relevant regulatory molecular mechanisms and interventions is still restricted. > With the rapid development of bioinformatics technology in recent years, we have gained greater insight into the understanding and treatment of atherosclerosis (AS), a complex disease involving the interaction of multiple genes, environmental factors and biological processes [7]. Through multi-omics studies, researchers have progressively identified a series of gene expression profiles, proteins, and biological processes associated with the onset and progression of AS [8,9]. Currently, there is limited research on ASO; therefore, further investigation into its pathogenesis and disease progression is crucial to explore more effective treatment modalities and enhance patients' quality of life and prognosis. In this study, we utilized the online GEO database to sift through gene expression data obtained from lower extremity arterial disease and control samples. Subsequently, we conducted a multi-algorithm joint analysis to identify potential key pathogenesis genes of ASO. Additionally, we conducted preliminary explorations into their related mechanisms through fundamental research. > Bruton tyrosine kinase (BTK) is a crucial non-receptor tyrosine kinase that impacts B-cell development, differentiation, and function.

[14] Molecular Pathogenesis of Endotheliopathy and Endotheliopathic Syndromes, Leading to Inflammation and Microthrombosis, and Various Hemostatic Clinical Phenotypes Based on “Two-Activation Theory of the Endothelium” and “Two-Path Unifying Theory” of Hemostasis

• Authors: Jae C Chang
• Year: 2022
• Venue: Medicina
• URL: https://www.semanticscholar.org/paper/69ea48751b7937c6f45b40b0475c14ce88da0e3a
• DOI: 10.3390/medicina58091311
• PMID: 36143988
• PMCID: 9504959
• Citations: 23
• Influential citations: 1
• Summary: Endotheliopathy is characterized by the increased activity of FVIII, overexpressed ULVWF/VWF antigen, and insufficient ADAMTS13 activity, which activates the UL VWF path of hemostasis, leading to consumptive thrombocytopenia and microthrombosis.
• Evidence snippets:
• Snippet 1 (score: 0.436) > Recognizing endotheliopathy as the underlying pathogenetic mechanism of a clinical disease is a difficult task to prove because no unique clinical feature can be identified to make its specific phenotype diagnosis.Each clinical and pathological disease is so variable, even amongst the same clinical disorders.However, a guideline is summarized in Table 5 to suspect or confirm endotheliopathy as the underlying pathologic process based on its clinical, laboratory, and molecular findings.Each clinical phenotype manifested by endotheliopathy is influenced by: (1) the primary pathology of inflammation and microthrombosis affecting the arterial or venous vascular system; (2) various organ and tissue localization by endothelial heterogeneity and/or the tropism of the external insult; (3) an additional secondary modifying pathology due to a genetic disorder, such as thrombophilia or von Willebrand disease, and an acquired disease, such as sepsis or polytrauma. > In the past, when we had not recognized the endothelial nature of the pathologic process in many diseases, imprecise terms such as polyarteritis nodosa, thromboangiitis obliterans, acrocyanosis, SLE, scleroderma, acute necrotizing fasciitis, Kawasaki disease, Raynaud's phenomenon, Buerger's disease, Fournier's disease, SPG, limb gangrene, gas gangrene, peripheral vascular ischemia, and diabetic gangrene, and so on, were used.It is about time for the clinician to redefine and reclassify many human diseases based on the taxonomic diversity by identifying endotheliopathy as a major pathologic entity that occurs as a result of abnormal hemostasis in vivo, with the consideration of the interaction amongst the etiologic, genetic, pathogenetic, and environmental variables.

[15] Chronic Ulcers in Thromboangiitis Obliterans (Buerger's Disease): Updating Epidemiology, Physiopathology, and Bosentan—A Novel Strategy of Therapy

• Authors: I. Maturana, J. Rodríguez, C. González, S. Bleda, J. Haro et al.
• Year: 2013
• Venue: Ulcers
• URL: https://www.semanticscholar.org/paper/1280ac56c27f0f29dd141359f537618dadff6406
• DOI: 10.1155/2013/230780
• Citations: 2
• Summary: It is concluded that the beneficial effects of bosentan on improving endothelial function, inflammatory processes, and selective vasodilatation of damaged vessels result in a clinical enhancement regarding healing and preventive digital ulcers in TAO patients.
• Evidence snippets:
• Snippet 1 (score: 0.432) > Thromboangiitis obliterans (TAO) or Buerger's disease is a thrombotic, occlusive, and nonatherosclerotic segmental vasculitis that affects small-and medium-sized arteries and veins which may involve distal vessel of upper and lower extremities.As a vasculitis, it is characterized by inflammation and fibrinoid necrosis of blood vessel walls. > Classically, various mechanisms have been implicated in its etiopathogenesis including cell-mediated inflammation, immune complex-mediated inflammation, and autoantibody-mediated inflammation [1].Recently, novel pathways have been described in physiopathology of the disease, though not completely well known.The endothelin-1 (ET-1) has been associated in these etiological processes, which can induce to endothelial cell activation causing complications such as vessel occlusion and tissue destruction [2]. > ET-1 is a potent vasoconstrictor peptide, which exerts its action by targeting two transmembrane receptors (ETA and ETB).ET-1 facilitates the proliferation of vascular smooth muscle cells, promotes monocytes via activation of the ETA, and contributes to matrix remodelling leading to the abnormal thickening of vessel walls [1][2][3].Raised levels of ET-1 have been described in different kind of systemic vasculitis as mixed cryoglobulinemia, secondary Raynaud's phenomenon [2], acute phase of Henoch-Schölein purpura, early stages of giant cell arteritis [1], Takayasu's arteritis, and Buerger's disease [3].This finding supports that ET-1 may act as marker of vascular damage [2,3].Other nonvasculitic entities as rheumatoid arthritis, systemic lupus erythematous, systemic sclerosis, pulmonary hypertension, or artherosclerosis have been also associated with high levels of ET-1 and have been related to vascular injury.Although data are limited, there is evidence suggesting that ET-1 plays a role in the clinical manifestations of vasculitis.

[16] Endothelial activation in thromboangiitis obliterans: mechanisms and therapeutic horizons

• Authors: Wanting Wang, Siyao Chang, Gang Zhao
• Year: 2025
• Venue: Frontiers in Immunology
• URL: https://www.semanticscholar.org/paper/fe1728a31d06a20048d8c2ac07b1208a603234d6
• DOI: 10.3389/fimmu.2025.1668203
• PMID: 40936931
• PMCID: 12420300
• Citations: 3
• Summary: This review summarizes the multifactorial pathogenesis of TAO, emphasizing EC activation as a therapeutic linchpin, and outlines future directions to bridge translational gaps in disease management.
• Evidence snippets:
• Snippet 1 (score: 0.428) > Thromboangiitis obliterans (TAO) is a chronic, non-atherosclerotic, segmental vasculitis characterized by inflammatory thrombi affecting small-and medium-sized arteries and veins of the extremities, often progressing to ulcers or gangrene (1). Arterial insufficiency leads to claudication, Raynaud's phenomenon, and, in severe cases, amputation. The distal distribution and poor collateral circulation render surgical and endovascular approaches largely ineffective. Although the precise pathogenesis remains unclear, accumulating evidence suggests an autoimmune component, with various autoantibodies and immune cells targeting vascular structures (2)(3)(4). Histologically, TAO features a cellular thrombus rich in polymorphonuclear leukocytes, mononuclear cells, and giant cells, with minimal vessel wall involvement (5). Conventional inflammatory markers (ESR, CRP) and common autoantibodies may remain normal during acute episodes, yet immune dysregulation is believed to drive disease activity (6). Autoimmune features are frequently observed, including elevated anti-endothelial cell antibodies (AECAs), especially during active disease. These antibodies bind not only to surface but also intracellular endothelial antigens, implicating endothelial dysfunction in disease progression (7). > Endothelial dysfunction in TAO is often preceded by endothelial activation, marked by increased expression of adhesion molecules such as ICAM-1 and VCAM-1, which promote leukocyte adhesion and a prothrombotic vascular phenotype. Elevated circulating ICAM-1 levels further support this persistent endothelial activation (8). This process is primarily mediated by pro-inflammatory cytokines-particularly TNF and IL-6-which enhance leukocyte recruitment and adherence to the endothelium (9). Thus, endothelial activation constitutes a central mechanism in TAO pathophysiology and represents a potential therapeutic target. This review highlights recent insights into the role of endothelial cell activation in TAO and its implications for future therapeutic interventions. > 2 Mechanisms of endothelial cell activation in TAO

[17] Leprosy Mimicking Thrombangiitis Obliterans (Buerger’s Disease): A Case Study

• Authors: C. O. Sena, I. M. B. Goulart, Pâmella C Justino Sena, Juliana C Justino Omar, Bruno C Dornelas
• Year: 2025
• Venue: Cureus
• URL: https://www.semanticscholar.org/paper/dbf239787e4284cae6eee83be220e78698558543
• DOI: 10.7759/cureus.80822
• PMID: 40255772
• PMCID: 12007437
• Citations: 1
• Summary: A rare case of atypical borderline lepromatous (BL) leprosy in a type 1 reaction with an initial presentation mimicking TAO in an elderly woman, which masked the diagnosis of BL leprosy.
• Evidence snippets:
• Snippet 1 (score: 0.422) > Thromboangiitis obliterans' pathophysiology remains incompletely understood, and its diagnosis primarily relies on a clinical assessment guided by epidemiological factors to approach ischemic limb phenomena [9,10]. Skin biopsy plays a critical role in excluding differential diagnoses of limb ischemia causes [7]. Based on clinical history and physical examination findings, the medical team initially considered Buerger's disease. Despite the patient's clinical features not aligning with typical TAO demographics (male smokers under 50 years), it was recognized that TAO can affect women over 50 years [11]. Skin biopsy serves as a diagnostic tool in cases involving large artery damage, individuals over 50 years, DM, positive antinuclear antibodies, high anticardiolipin antibodies, subcutaneous nodules, or superficial thrombophlebitis [12]. Microscopic changes in TAO vary across clinical stages: the acute phase reveals an inflammatory occlusive thrombus composed of polymorphonuclear leukocytes, multinucleated giant cells, and microabscesses [10]; > during the intermediate phase, inflammatory thrombus progresses to organization, and in the chronic phase, the inflammatory response regresses and thrombus fibrosis [10,12]. However, our case did not exhibit signs of vasculitis in the skin biopsy. > Leprosy's pathophysiology is comparatively better understood and directly reflects variation in host immune responses to mycobacterial infection. In the lepromatous spectrum, the high bacillary load and abundant PGL-I and lipoarabinomannan (LAM) antigens suppress macrophage activity, facilitating bacterial survival, replication, and disease progression [13][14][15].

[18] Endothelial cell iron overload and ferroptosis mediate thrombosis and inflammation through the miR-32-5p/neurofibromin 2 pathway

• Authors: Ying Deng, Xueguang Lin, Jun Wei, Bo Chen, Huafang Yan et al.
• Year: 2025
• Venue: European Journal of Medical Research
• URL: https://www.semanticscholar.org/paper/19b852bd22e18ebdff0bcbea662a3c529fa0ba07
• DOI: 10.1186/s40001-025-02716-y
• PMID: 40481609
• PMCID: 12142838
• Citations: 3
• Summary: It is demonstrated that iron overload and ferroptosis are key risk factors in patients with TAO and that the exosomal miR-32-5p/NF2 pathway may play an important role in TAO pathogenesis.
• Evidence snippets:
• Snippet 1 (score: 0.416) > Thromboangiitis obliterans (TAO), also known as Buerger's disease, is a nonatherosclerotic peripheral vascular disease mediated by immune dysregulation. Clinically, TAO is characterized by obvious thrombosis, occlusion, segmental, and inflammation [1]. As TAO progresses, pain and gangrene can continue to deteriorate, and the amputation rate of patients with 20 years of disease is as high as 46% [2]. Smoking cessation and revascularization surgery can control and relieve the clinical symptoms of such patients [3]. Studies have shown that vascular endothelial cell injury and immune system abnormality are the key risk factors in TAO pathogenesis, but the mechanism remains unclear [4,5]. > Accumulation of iron has been implicated in atherosclerotic and nonatherosclerotic peripheral vascular disease. In cardiovascular diseases, iron overload markedly enhances the thrombosis process via reactive oxygen species and endothelial cell death [6]. Ferroptosis is a form of programmed cell death that is caused by iron overload [7]. In addition to promoting excess free iron, ferroptosis is associated with lipid peroxidation and restricted glutathione peroxidase 4 (GPX4) activity, among others [8,9]. Iron overload and key ferroptosis-related genes, such as heme oxygenase 1 (HMOX1) and SLC7 A11, are significantly increased in arterial plaques [10,11]. GPX4 has been shown to be decreased in the severe stage of plaque [12]. Iron restriction and ferroptosis inhibitors could significantly decrease plaque formation [13][14][15]. The recent studies have shown that malondialdehyde (MDA), Ferritin light chain (FTL), and Ferritin heavy chain 1 (FTH1) are increased in the intestinal tissues of patients with intestinal Behçet's syndrome [16]. Thus, iron metabolism and ferroptosis may play an important role in TAO.

[19] Exploring Causal Relationships between Circulating Inflammatory Proteins and Thromboangiitis Obliterans: A Mendelian Randomization Study

• Authors: Bihui Zhang, Rui He, Ziping Yao, Pengyu Li, Guo-chen Niu et al.
• Year: 2023
• Venue: Thrombosis and Haemostasis
• URL: https://www.semanticscholar.org/paper/9ab02b9088b5df20682fe208a10f7b44a6ad10ce
• DOI: 10.1055/s-0044-1786809
• PMID: 38788766
• PMCID: 11518616
• Citations: 2
• Influential citations: 1
• Summary: C–C motif chemokine 4 and glial cell line-derived neurotrophic factor are identified as potential protective biomarkers for TAO, whereas C–C motif chemokine 23 emerges as a suggestive risk marker.
• Evidence snippets:
• Snippet 1 (score: 0.415) > Thromboangiitis obliterans (TAO), commonly referred to as Buerger's disease, is a distinct nonatherosclerotic, segmental inflammatory disorder that predominantly affects small-and medium-sized arteries and veins in both the upper and lower extremities. 1 TAO, with an annual incidence of 12.6 per 100,000 in the United States, is observed worldwide but is more prevalent in the Middle East and Far East. 1 The disease typically presents in patients <45 years of age. Despite over a century of recognition, advancements in comprehending its etiology, pathophysiology, and optimal treatment strategies have been limited. 2,3 Vascular event-free survival and amputation-free survival rates at 5, 10, and 15 years are reported at 41 and 85%, 23 and 74%, and 19 and 66%, respectively. 4 n immune-mediated response is implicated in TAO pathogenesis. 5 Recent studies have identified a balanced presence of CD4þ and CD8þ T cells near the internal lamina. Additionally, macrophages and S100þ dendritic cells are present in thrombi and intimal layers. 5,6 Elevated levels of diverse cytokines in TAO patients highlight the critical importance of inflammatory and autoimmune mechanisms. 2,7 Nonetheless, the clinical significance of these cytokines is yet to be fully understood, due to the scarcity of comprehensive experimental and clinical studies. Investigating circulating inflammatory proteins could shed light on the biological underpinnings of TAO, offering new diagnostic and therapeutic avenues. > Mendelian randomization (MR) is an approach that leverages genetic variants associated with specific exposures to infer causal relationships between risk factors and disease outcomes. 8 This method, which relies on the random distribution of genetic variants during meiosis, helps minimize confounding factors and biases inherent in environmental or behavioral influences. 9 It is particularly useful in addressing limitations of conventional observational studies and randomized controlled trials, especially for rare diseases like TAO. 10 For a robust MR analysis, three critical assumptions must be met: the genetic variants should be strongly associated with the risk factor, not linked to confounding variables, and affect the outcome solely through the risk factor, excluding any direct causal pathways. 10

Notes

• This provider combines search_papers_by_relevance with snippet_search.
• No synthesis or second-stage model call is performed.