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name: Essential Hypertension
creation_date: '2025-12-18T17:01:35Z'
updated_date: '2026-02-17T21:53:14Z'
category: Complex
parents:
- Cardiovascular Disease
disease_term:
preferred_term: essential hypertension
term:
id: MONDO:0001134
label: essential hypertension
pathophysiology:
- name: Vascular Resistance
description: >
Increased systemic vascular resistance due to structural and functional
changes in resistance arterioles. Endothelial dysfunction, vascular
remodeling, and increased smooth muscle tone contribute.
cell_types:
- preferred_term: Vascular Smooth Muscle Cell
term:
id: CL:0000359
label: vascular associated smooth muscle cell
- preferred_term: Endothelial Cell
term:
id: CL:0000115
label: endothelial cell
biological_processes:
- preferred_term: Blood Pressure Regulation
term:
id: GO:0008217
label: regulation of blood pressure
evidence:
- reference: PMID:37080965
reference_title: "Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions."
supports: SUPPORT
snippet: "The alterations in signaling pathways in these cells are the key molecular
mechanisms underlying vascular dysfunction and hypertension development."
explanation: This supports the central role of vascular dysfunction in
hypertension pathophysiology.
- reference: PMID:38172242
reference_title: "Immune and inflammatory mechanisms in hypertension."
supports: SUPPORT
snippet: "Effector mediators impair nitric oxide bioavailability, leading to endothelial
dysfunction and increased vascular contractility."
explanation: This describes the mechanism by which endothelial dysfunction
increases vascular resistance.
- reference: PMID:36703963
reference_title: "Role of inflammation, immunity, and oxidative stress in hypertension: New insights and potential therapeutic targets."
supports: SUPPORT
snippet: "Both innate and adaptive immunity are now known to promote the elevation
of blood pressure by triggering vascular inflammation and microvascular remodeling."
explanation: This confirms the role of vascular remodeling in increasing
resistance.
- name: Renin-Angiotensin-Aldosterone System Dysregulation
description: >
Overactivation of the RAAS leads to sodium retention, vasoconstriction,
and vascular remodeling, all contributing to elevated blood pressure.
cell_types:
- preferred_term: Kidney Granular Cell
term:
id: CL:0000648
label: kidney granular cell
biological_processes:
- preferred_term: RAAS Pathway
term:
id: GO:0002018
label: renin-angiotensin regulation of aldosterone production
evidence:
- reference: PMID:39765782
reference_title: "Oxidative Stress in Kidney Injury and Hypertension."
supports: SUPPORT
snippet: "Activation of intrarenal angiotensin II receptors contributes to sodium
retention and high BP."
explanation: This directly supports RAAS activation causing sodium retention
and elevated blood pressure.
- reference: PMID:39765782
reference_title: "Oxidative Stress in Kidney Injury and Hypertension."
supports: SUPPORT
snippet: "Oxidative stress, inflammation, and activation of the renin-angiotensin-aldosterone
system (RAAS) play critical roles in causing kidney injury in HTN."
explanation: This confirms RAAS activation as a critical mechanism in
hypertension.
- reference: PMID:37080965
reference_title: "Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions."
supports: SUPPORT
snippet: "In this manuscript, we will comprehensively review the signaling pathways
involved in vascular function regulation and hypertension progression, including
calcium pathway, NO-NOsGC-cGMP pathway, various vascular remodeling pathways
and some important upstream pathways such as renin-angiotensin-aldosterone system,
oxidative stress-related signaling pathway, immunity/inflammation pathway, etc."
explanation: This confirms RAAS as a key upstream pathway driving
hypertension.
- name: Sympathetic Nervous System Overactivity
description: >
Enhanced sympathetic tone increases heart rate, cardiac output, and
peripheral vascular resistance through catecholamine release.
evidence:
- reference: PMID:38172242
reference_title: "Immune and inflammatory mechanisms in hypertension."
supports: PARTIAL
snippet: "Neoantigens, the NLRP3 inflammasome and increased sympathetic outflow,
as well as cytokines (including IL-6, IL-7, IL-15, IL-18 and IL-21) and a high-salt
environment, can contribute to immune activation in hypertension."
explanation: This supports sympathetic involvement in hypertension but only
partially supports the full physiologic descriptor.
- name: Immune and Inflammatory Activation
description: >
Chronic immune activation involving both innate and adaptive immunity drives
vascular inflammation and remodeling. T cells, monocytes, macrophages, and
dendritic cells infiltrate target organs including arteries, kidneys, heart,
and brain, releasing proinflammatory cytokines such as IL-17, IFN-gamma, and
TNF-alpha that elevate blood pressure and cause end-organ damage.
cell_types:
- preferred_term: T Cell
term:
id: CL:0000084
label: T cell
- preferred_term: Macrophage
term:
id: CL:0000235
label: macrophage
- preferred_term: Dendritic Cell
term:
id: CL:0000451
label: dendritic cell
biological_processes:
- preferred_term: Inflammatory Response
term:
id: GO:0006954
label: inflammatory response
evidence:
- reference: PMID:38172242
reference_title: "Immune and inflammatory mechanisms in hypertension."
supports: SUPPORT
snippet: "T cells, monocytes, macrophages, dendritic cells, B cells and natural
killer cells are all implicated in hypertension."
explanation: This establishes the broad involvement of immune cells in
hypertension.
- reference: PMID:38172242
reference_title: "Immune and inflammatory mechanisms in hypertension."
supports: SUPPORT
snippet: "The activated immune cells migrate to target organs such as arteries
(especially the perivascular fat and adventitia), kidneys, the heart and the
brain, where they release effector cytokines that elevate blood pressure and
cause vascular remodelling, renal damage, cardiac hypertrophy, cognitive impairment
and dementia."
explanation: This describes how immune cell infiltration leads to target
organ damage in hypertension.
- reference: PMID:36703963
reference_title: "Role of inflammation, immunity, and oxidative stress in hypertension: New insights and potential therapeutic targets."
supports: SUPPORT
snippet: "Hypertension is regarded as the most prominent risk factor for cardiovascular
diseases, which have become a primary cause of death, and recent research has
demonstrated that chronic inflammation is involved in the pathogenesis of hypertension."
explanation: This confirms the role of chronic inflammation in hypertension
pathogenesis.
- reference: PMID:38164753
reference_title: "Recent Advances in Understanding Peripheral and Gut Immune Cell-Mediated Salt-Sensitive Hypertension and Nephropathy."
supports: SUPPORT
snippet: "Elevated sodium activates antigen-presenting cells to release proinflammatory
cytokines including IL (interleukin) 6, tumor necrosis factor-α, IL-1β, and
accumulate isolevuglandin-protein adducts. In turn, these activate T cells release
prohypertensive cytokines including IL-17A."
explanation: This describes the salt-sensitive immune activation pathway
driving hypertension.
- name: Oxidative Stress
description: >
Increased production of reactive oxygen species (ROS) by NADPH oxidases
and decreased antioxidant defenses lead to oxidative stress. ROS impair
nitric oxide bioavailability, promote endothelial dysfunction, and activate
inflammatory pathways, all contributing to elevated blood pressure and
kidney injury.
biological_processes:
- preferred_term: ROS Metabolic Process
term:
id: GO:0072593
label: reactive oxygen species metabolic process
evidence:
- reference: PMID:39765782
reference_title: "Oxidative Stress in Kidney Injury and Hypertension."
supports: NO_EVIDENCE
snippet: "Overproduction of reactive oxygen species (ROS) plays a crucial role
in the development and progression of HTN, impacting renal function and BP regulation."
explanation: This establishes the central role of ROS in hypertension
development.
- reference: PMID:39765782
reference_title: "Oxidative Stress in Kidney Injury and Hypertension."
supports: SUPPORT
snippet: "Targeting specific NADPH oxidase (NOX) isoforms to inhibit ROS production
and enhance antioxidant mechanisms may improve renal structure and function
while lowering blood pressure."
explanation: This confirms NOX enzymes as key sources of pathogenic ROS in
hypertension.
- reference: PMID:36703963
reference_title: "Role of inflammation, immunity, and oxidative stress in hypertension: New insights and potential therapeutic targets."
supports: SUPPORT
snippet: "In particular, interferon-gamma (IFN-γ) and interleukin-17 (IL-17) produced
by activated T lymphocytes contribute to hypertension by inducing oxidative
stress injury and endothelial dysfunction."
explanation: This describes how immune activation leads to oxidative stress
and endothelial dysfunction.
phenotypes:
- name: Elevated Blood Pressure
category: Cardiovascular
frequency: VERY_FREQUENT
diagnostic: true
phenotype_term:
preferred_term: Hypertension
term:
id: HP:0000822
label: Hypertension
evidence:
- reference: PMID:38172242
reference_title: "Immune and inflammatory mechanisms in hypertension."
supports: SUPPORT
snippet: "Hypertension is a global health problem, with >1.3 billion individuals
with high blood pressure worldwide."
explanation: This establishes hypertension as the defining diagnostic
feature of the condition.
- reference: PMID:38164753
reference_title: "Recent Advances in Understanding Peripheral and Gut Immune Cell-Mediated Salt-Sensitive Hypertension and Nephropathy."
supports: SUPPORT
snippet: "Hypertension is the primary modifiable risk factor for cardiovascular,
renal, and cerebrovascular diseases and is considered the main contributing
factor to morbidity and mortality worldwide."
explanation: This confirms the clinical significance of elevated blood
pressure as the primary phenotype.
- name: Headache
category: Neurological
frequency: OCCASIONAL
phenotype_term:
preferred_term: Headache
term:
id: HP:0002315
label: Headache
- name: Left Ventricular Hypertrophy
category: Cardiovascular
frequency: FREQUENT
notes: Secondary to chronic pressure overload
phenotype_term:
preferred_term: Left Ventricular Hypertrophy
term:
id: HP:0001712
label: Left ventricular hypertrophy
evidence:
- reference: PMID:38172242
reference_title: "Immune and inflammatory mechanisms in hypertension."
supports: SUPPORT
snippet: "The activated immune cells migrate to target organs such as arteries
(especially the perivascular fat and adventitia), kidneys, the heart and the
brain, where they release effector cytokines that elevate blood pressure and
cause vascular remodelling, renal damage, cardiac hypertrophy, cognitive impairment
and dementia."
explanation: This confirms cardiac hypertrophy as a consequence of chronic
hypertension and immune-mediated damage.
- name: Renal Damage
category: Renal
frequency: FREQUENT
notes: Hypertensive nephropathy and chronic kidney disease
phenotype_term:
preferred_term: Renal Insufficiency
term:
id: HP:0000083
label: Renal insufficiency
evidence:
- reference: PMID:39765782
reference_title: "Oxidative Stress in Kidney Injury and Hypertension."
supports: SUPPORT
snippet: "Hypertension (HTN) is a major contributor to kidney damage, leading
to conditions such as nephrosclerosis and hypertensive nephropathy, significant
causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD)."
explanation: This confirms renal damage as a major consequence of chronic
hypertension.
- reference: PMID:38172242
reference_title: "Immune and inflammatory mechanisms in hypertension."
supports: SUPPORT
snippet: "The activated immune cells migrate to target organs such as arteries
(especially the perivascular fat and adventitia), kidneys, the heart and the
brain, where they release effector cytokines that elevate blood pressure and
cause vascular remodelling, renal damage, cardiac hypertrophy, cognitive impairment
and dementia."
explanation: This describes immune-mediated renal damage as a consequence of
hypertension.
- reference: PMID:38164753
reference_title: "Recent Advances in Understanding Peripheral and Gut Immune Cell-Mediated Salt-Sensitive Hypertension and Nephropathy."
supports: SUPPORT
snippet: "Human and animal studies demonstrate that the immune system plays an
important role in the etiology and pathogenesis of salt sensitivity of blood
pressure, kidney damage, and vascular diseases."
explanation: This confirms the role of immune mechanisms in causing kidney
damage in hypertension.
genetic:
- name: ACE
association: Risk Factor
evidence:
- reference: PMID:39765782
reference_title: "Oxidative Stress in Kidney Injury and Hypertension."
supports: SUPPORT
snippet: "Genetic and environmental factors influence the susceptibility to hypertensive
renal damage, with African American populations having a higher tendency due
to genetic variants."
explanation: Snippet supports genetic susceptibility broadly, but does not
provide ACE-specific evidence.
- name: AGT
association: Risk Factor
evidence:
- reference: PMID:39765782
reference_title: "Oxidative Stress in Kidney Injury and Hypertension."
supports: NO_EVIDENCE
snippet: "Genetic and environmental factors influence the susceptibility to hypertensive
renal damage, with African American populations having a higher tendency due
to genetic variants."
explanation: Snippet supports genetic susceptibility broadly, but does not
provide AGT-specific evidence.
- name: ADD1
association: Risk Factor
environmental:
- name: High Sodium Diet
notes: Major modifiable risk factor
evidence:
- reference: PMID:38164753
reference_title: "Recent Advances in Understanding Peripheral and Gut Immune Cell-Mediated Salt-Sensitive Hypertension and Nephropathy."
supports: SUPPORT
snippet: "Approximately 50% of hypertensive and 25% of normotensive people exhibit
salt sensitivity of blood pressure, which is an independent risk factor for
cardiovascular disease."
explanation: This establishes high salt intake as a major environmental risk
factor driving salt-sensitive hypertension.
- reference: PMID:38164753
reference_title: "Recent Advances in Understanding Peripheral and Gut Immune Cell-Mediated Salt-Sensitive Hypertension and Nephropathy."
supports: SUPPORT
snippet: "Moreover, high-salt intake is associated with gut dysbiosis, leading
to inflammation, oxidative stress, and blood pressure elevation but the mechanistic
contribution to salt-sensitivity of blood pressure is not clearly understood."
explanation: This describes how high salt intake promotes hypertension
through immune and inflammatory mechanisms.
- reference: PMID:38172242
reference_title: "Immune and inflammatory mechanisms in hypertension."
supports: SUPPORT
snippet: "Neoantigens, the NLRP3 inflammasome and increased sympathetic outflow,
as well as cytokines (including IL-6, IL-7, IL-15, IL-18 and IL-21) and a high-salt
environment, can contribute to immune activation in hypertension."
explanation: This confirms high-salt environment contributes to immune
activation driving hypertension.
- name: Obesity
notes: Strong association with elevated blood pressure
evidence:
- reference: PMID:38172242
reference_title: "Immune and inflammatory mechanisms in hypertension."
supports: SUPPORT
snippet: "These mechanisms link hypertension with obesity, autoimmunity, periodontitis
and COVID-19."
explanation: This confirms obesity is mechanistically linked to hypertension
through shared inflammatory pathways.
- name: Chronic Stress
notes: Contributes to sympathetic overactivity
- name: Alcohol Consumption
notes: Excessive intake raises blood pressure
treatments:
- name: ACE Inhibitors
description: Block angiotensin-converting enzyme to reduce vasoconstriction
and sodium retention.
evidence:
- reference: PMID:39765782
reference_title: "Oxidative Stress in Kidney Injury and Hypertension."
supports: PARTIAL
snippet: "Managing blood pressure (BP) effectively with treatments targeting RAAS
activation, oxidative stress, and inflammation is crucial in preventing renal
damage and the progression of HTN-related CKD and ESRD."
explanation: Supports RAAS-targeting treatment strategy in general, but does
not directly name ACE inhibitors.
- name: Angiotensin Receptor Blockers
description: Block AT1 receptors to reduce RAAS effects.
evidence:
- reference: PMID:39765782
reference_title: "Oxidative Stress in Kidney Injury and Hypertension."
supports: PARTIAL
snippet: "Managing blood pressure (BP) effectively with treatments targeting RAAS
activation, oxidative stress, and inflammation is crucial in preventing renal
damage and the progression of HTN-related CKD and ESRD."
explanation: Supports RAAS-targeting treatment strategy in general, but does
not directly name ARBs.
- name: Calcium Channel Blockers
description: Reduce vascular smooth muscle contraction.
evidence:
- reference: PMID:37080965
reference_title: "Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions."
supports: NO_EVIDENCE
snippet: "Meanwhile, we will also summarize the treatment methods of hypertension
that targets vascular function regulation and discuss the possibility of these
signaling pathways being applied to clinical work."
explanation: Snippet states that treatments are reviewed, but does not
provide direct evidence for calcium channel blockers.
- name: Thiazide Diuretics
description: Promote sodium excretion to reduce blood volume.
evidence:
- reference: PMID:39765782
reference_title: "Oxidative Stress in Kidney Injury and Hypertension."
supports: NO_EVIDENCE
snippet: "Anti-natriuretic mechanisms can reset the pressure-natriuresis relationship,
requiring a higher BP to excrete sodium matched to intake."
explanation: Snippet describes sodium-handling pathophysiology, not direct
evidence for thiazide diuretic treatment.
- name: Beta Blockers
description: Reduce heart rate and cardiac output.
- name: Lifestyle Modification
description: Dietary changes (DASH diet, sodium restriction), exercise, weight
loss.
evidence:
- reference: PMID:38164753
reference_title: "Recent Advances in Understanding Peripheral and Gut Immune Cell-Mediated Salt-Sensitive Hypertension and Nephropathy."
supports: NO_EVIDENCE
snippet: "Approximately 50% of hypertensive and 25% of normotensive people exhibit
salt sensitivity of blood pressure, which is an independent risk factor for
cardiovascular disease."
explanation: Snippet supports salt sensitivity epidemiology, not direct
efficacy evidence for lifestyle modification.
classifications:
harrisons_chapter:
- classification_value: CARDIOVASCULAR
datasets:
references:
- reference: DOI:10.1038/s41392-023-01430-7
title: 'Signaling pathways in vascular function and hypertension: molecular mechanisms
and therapeutic interventions'
findings: []
- reference: DOI:10.1038/s41569-023-00964-1
title: Immune and inflammatory mechanisms in hypertension
findings: []
- reference: DOI:10.1038/s41581-024-00838-w
title: Immune mechanisms in the pathophysiology of hypertension
findings: []
- reference: DOI:10.1161/hypertensionaha.123.22031
title: Recent Advances in Understanding Peripheral and Gut Immune
Cell-Mediated Salt-Sensitive Hypertension and Nephropathy
findings: []
- reference: DOI:10.3389/fimmu.2022.1098725
title: 'Role of inflammation, immunity, and oxidative stress in hypertension: New
insights and potential therapeutic targets'
findings: []
- reference: DOI:10.3390/antiox13121454
title: Oxidative Stress in Kidney Injury and Hypertension
findings: []
Disease Pathophysiology Research Report
Target Disease - Disease Name: Essential Hypertension (primary arterial hypertension) - MONDO ID: MONDO:0004979 - Category: Complex
Pathophysiology description (narrative) Essential hypertension arises from the integration of renal sodium retention and intrarenal RAAS upregulation, endothelial nitric oxide (NO) deficiency with oxidative stress, sympathetic nervous system activation, and sterile low-grade inflammation driven by both innate and adaptive immune pathways. These processes promote microvascular dysfunction, vascular remodeling and stiffness, and altered pressure–natriuresis, culminating in sustained elevation of arterial pressure and target-organ damage in kidney, heart, vasculature, and brain (kidney–heart–brain–gut cross-talk) (zhang2023roleofinflammation pages 2-3, ma2023signalingpathwaysin pages 15-16, guzik2024immuneandinflammatory pages 1-4).
Direct expert quotes supporting core concepts - “Activated immune cells migrate to arteries (perivascular fat and adventitia), kidneys, heart and brain, where effector cytokines promote vascular remodelling, endothelial dysfunction (via decreased nitric oxide bioavailability), increased vascular contractility, [and] altered renal sodium and water handling” (Nature Reviews Cardiology, Jan 2024). URL: https://doi.org/10.1038/s41569-023-00964-1 (guzik2024immuneandinflammatory pages 1-4) - “Activation of intrarenal angiotensin II receptors contributes to sodium retention and high BP… Overproduction of reactive oxygen species (ROS) plays a crucial role in the development and progression of HTN, impacting renal function and BP regulation” (Antioxidants, Nov 2024). URL: https://doi.org/10.3390/antiox13121454 (arendshorst2024oxidativestressin pages 7-9, arendshorst2024oxidativestressin pages 5-7) - “Sodium activates human monocytes via the NADPH oxidase and isolevuglandin formation… Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction” (Hypertension, Mar 2024). URL: https://doi.org/10.1161/hypertensionaha.123.22031 (saleem2024recentadvancesin pages 10-11)
1) Core Pathophysiology - Renal–RAAS and pressure–natriuresis reset: Intrarenal Ang II (AGT→REN→ACE→Ang II→AGTR1) promotes antinatriuresis, reduces renal blood flow and GFR, and shifts pressure–natriuresis rightward; endothelin-1 (EDN1) augments vasoconstriction, oxidative stress, and renal/vascular remodeling (arendshorst2024oxidativestressin pages 5-7, arendshorst2024oxidativestressin pages 7-9). - Endothelial dysfunction and NO–ROS imbalance: Reduced NOS3-derived NO, increased NOX1/NOX2(CYBB)/NOX4-derived ROS, and decreased SOD/CAT lead to NO scavenging, eNOS uncoupling, vasoconstriction, and inflammation (zhang2023roleofinflammation pages 2-3, arendshorst2024oxidativestressin pages 7-9, arendshorst2024oxidativestressin pages 5-7). - Sympathetic activation: Elevated central sympathetic outflow increases vascular tone and renal renin release, contributing to sustained hypertension and nocturnal/non-dipping phenotypes (ma2023signalingpathwaysin pages 15-16). - Immune/inflammation: NLRP3 inflammasome and cytokines (IL‑1β, IL‑6, TNF) drive chronic vascular–renal inflammation; Th17/IL‑17A and antigen-presenting cell activation amplify hypertension and vascular dysfunction (guzik2024immuneandinflammatory pages 1-4, saleem2024recentadvancesin pages 10-11). - Salt sensitivity and gut–immune axis: High salt injures endothelial glycocalyx and increases ENaC-mediated Na+ entry in APCs/endothelium → PKC–NOX activation → IsoLG adducts presented to T cells → IL‑17A/TNF/IFNγ release; concurrent gut dysbiosis alters SCFA signaling (FFAR2/FFAR3/HCAR2) and promotes pro-hypertensive inflammation (saleem2024recentadvancesin pages 19-22, saleem2024recentadvancesin pages 10-11). - Vascular remodeling and stiffness: TGF‑β/SMAD signaling and MMP activity drive ECM deposition, media–adventitia remodeling, and increased pulse wave velocity; oxidative stress and inflammation accelerate stiffening (ma2023signalingpathwaysin pages 15-16, arendshorst2024oxidativestressin pages 7-9). - Genetics and kidney-omics: BP polygenicity implicates vascular and renal genes (e.g., NOS3, ATP2B1, SH2B3, SLC4A7); kidney transcriptome/proteome integration highlights renal pathways controlling sodium handling and downstream circulating mediators (ma2023signalingpathwaysin pages 15-16, zhang2023roleofinflammation pages 2-3).
2) Key Molecular Players - Genes/Proteins (HGNC): AGT, REN, ACE, AGTR1/AGTR2; EDN1/EDNRA/EDNRB; NOS3; NOX1, CYBB/NOX2, NOX4; SOD1/2/3, CAT; IL17A, IL6, TNF, IL1B, NLRP3; SCNN1A/B/G (ENaC), SLC12A3 (NCC), WNK1/WNK4, SGK1; ADRB1/ADRB2; TGFB1, SMAD2/SMAD3, MMP2/MMP9; ATP2B1, SH2B3, SLC4A7 (arendshorst2024oxidativestressin pages 7-9, arendshorst2024oxidativestressin pages 5-7, saleem2024recentadvancesin pages 19-22, saleem2024recentadvancesin pages 11-12, guzik2024immuneandinflammatory pages 1-4, zhang2023roleofinflammation pages 2-3, ma2023signalingpathwaysin pages 15-16). - Chemical Entities (CHEBI): Short-chain fatty acids—acetate (CHEBI:15366), propionate (CHEBI:17277), butyrate (CHEBI:17968)—modulate BP via FFAR2/FFAR3/HCAR2 signaling; isolevuglandins (IsoLGs) are reactive lipid aldehydes forming antigenic adducts in high-salt conditions (saleem2024recentadvancesin pages 19-22, saleem2024recentadvancesin pages 10-11). - Cell Types (CL): Endothelial cells, vascular smooth muscle cells (VSMCs), renal tubular epithelial cells (principal cells, DCT), juxtaglomerular cells, dendritic cells (CD11c+), monocytes/macrophages, Th17 T cells (guzik2024immuneandinflammatory pages 1-4, saleem2024recentadvancesin pages 19-22, saleem2024recentadvancesin pages 11-12, arendshorst2024oxidativestressin pages 5-7). - Anatomical Locations (UBERON): Kidney (UBERON:0002113), renal medulla (UBERON:0001225), vasculature (UBERON:0002049), aorta (UBERON:0000947), heart (UBERON:0000948), brain paraventricular nucleus (PVN; UBERON:0001898), gut (UBERON:0001555) (ma2023signalingpathwaysin pages 15-16, guzik2024immuneandinflammatory pages 1-4, saleem2024recentadvancesin pages 19-22).
| Category | Entity name | Standard ID (HGNC/GO/CL/UBERON/CHEBI) | Role / description | Mechanistic pathway(s) | Key cell types (CL) | Key anatomical sites (UBERON) | Supporting evidence (citation IDs) |
|---|---|---|---|---|---|---|---|
| RAAS — ligand | AGT (angiotensinogen) | HGNC:AGT | Liver-produced precursor of angiotensin I; substrate for REN → Ang II generation | Renin–angiotensin–aldosterone system (RAAS): REN → AGT → ACE → Ang II → AGTR1/2 | Hepatocytes (source); juxtaglomerular cells (REN) | Kidney (UBERON:0002113); Vasculature (UBERON:0002049) | (arendshorst2024oxidativestressin pages 5-7, zhang2023roleofinflammation pages 2-3) |
| RAAS — enzyme | REN (renin) | HGNC:REN | Protease from juxtaglomerular cells that cleaves AGT to Ang I; key regulator of RAAS activity | RAAS activation; pressure–natriuresis resetting | Juxtaglomerular (JG) cells | Kidney (UBERON:0002113) | (arendshorst2024oxidativestressin pages 5-7, zhang2023roleofinflammation pages 2-3) |
| RAAS — enzyme | ACE (angiotensin converting enzyme) | HGNC:ACE | Converts Ang I → Ang II; ACE inhibitors lower BP | RAAS → Ang II → AGTR1-mediated vasoconstriction and ROS production | Endothelial cells | Vasculature (UBERON:0002049); Lung endothelium | (arendshorst2024oxidativestressin pages 5-7, ma2023signalingpathwaysin pages 15-16) |
| RAAS — receptor | AGTR1 / AGTR2 (AT1/AT2) | HGNC:AGTR1, HGNC:AGTR2 | G-protein receptors mediating Ang II vasoconstriction (AT1) and counter-regulatory effects (AT2) | AGTR1 → NADPH oxidase activation → vasoconstriction, inflammation | Vascular smooth muscle cells (VSMC), renal tubular cells | Vasculature (UBERON:0002049); Kidney (UBERON:0002113) | (arendshorst2024oxidativestressin pages 5-7, ma2023signalingpathwaysin pages 15-16) |
| Endothelin system | EDN1 / EDNRA / EDNRB (ET-1, ETA, ETB) | HGNC:EDN1, HGNC:EDNRA, HGNC:EDNRB | Potent vasoconstrictor peptide (ET-1) and receptors mediating vasoconstriction, inflammation and remodeling | ET-1 → ETA/ETB → VSMC contraction and fibrosis; cross-talk with MMP/TGFβ pathways | Endothelial cells (produce ET-1); VSMC (respond) | Vasculature (UBERON:0002049); Aorta (UBERON:0000947) | (arendshorst2024oxidativestressin pages 7-9, ma2023signalingpathwaysin pages 15-16) |
| Nitric oxide synthase | NOS3 (eNOS) | HGNC:NOS3 | Endothelial-derived NO synthase producing NO to maintain vasodilation and inhibit inflammation | NO → sGC–cGMP vasodilation; eNOS uncoupling → ROS and endothelial dysfunction | Endothelial cells | Vasculature (UBERON:0002049); Heart (UBERON:0000948) | (zhang2023roleofinflammation pages 2-3, ma2023signalingpathwaysin pages 15-16) |
| NADPH oxidases (ROS sources) | NOX1, CYBB/NOX2, NOX4 | HGNC:NOX1, HGNC:CYBB (NOX2), HGNC:NOX4 | Enzymes generating ROS (superoxide/H2O2) that reduce NO bioavailability and drive inflammation/remodeling | NOX → ROS → NO scavenging; NLRP3 activation; fibrosis pathways | VSMC, endothelial cells, renal tubular cells, immune cells | Kidney (UBERON:0002113); Vasculature (UBERON:0002049) | (arendshorst2024oxidativestressin pages 7-9, arendshorst2024oxidativestressin pages 5-7, zhang2023roleofinflammation pages 2-3) |
| Antioxidant defenses | SOD1 / SOD2 / SOD3, CAT | HGNC:SOD1, HGNC:SOD2, HGNC:SOD3, HGNC:CAT | Enzymes detoxifying ROS (superoxide dismutases, catalase); loss increases oxidative stress and BP | Antioxidant loss → enhanced NOX-driven ROS → endothelial dysfunction and inflammation | Endothelial cells; mitochondria-rich renal tubular cells | Kidney (UBERON:0002113); Vasculature (UBERON:0002049) | (arendshorst2024oxidativestressin pages 7-9, arendshorst2024oxidativestressin pages 5-7) |
| Inflammatory cytokines / inflammasome | IL17A, IL6, TNF, IL1B, NLRP3 | HGNC:IL17A, HGNC:IL6, HGNC:TNF, HGNC:IL1B, HGNC:NLRP3 | Cytokines and inflammasome mediating vascular inflammation, T-cell–driven hypertension and end-organ fibrosis | Th17 → IL-17A; NLRP3 → IL-1β/IL-18 → chronic inflammation → vascular and renal injury | T cells (Th17, CD4+), macrophages, dendritic cells | Perivascular adipose/adventitia (UBERON:0002049); Kidney (UBERON:0002113) | (guzik2024immuneandinflammatory pages 1-4, saleem2024recentadvancesin pages 19-22, saleem2024recentadvancesin pages 10-11) |
| Renal epithelial transport — ENaC | SCNN1A / SCNN1B / SCNN1G (ENaC α/β/γ) | HGNC:SCNN1A, HGNC:SCNN1B, HGNC:SCNN1G | Apical epithelial Na+ channel in distal nephron; aldosterone/cleavage increases Na+ reabsorption and extracellular volume | ENaC activation (aldosterone / MR) → increased Na+ retention → volume-dependent hypertension; immune/salt modulation via ENaC in APCs/endothelium | Principal cells; collecting duct epithelial cells | Kidney distal nephron / collecting duct (UBERON:0002113) | (saleem2024recentadvancesin pages 11-12, saleem2024recentadvancesin pages 19-22) |
| Renal epithelial transport — NCC & regulators | SLC12A3 (NCC); WNK1 / WNK4; SGK1 | HGNC:SLC12A3, HGNC:WNK1, HGNC:WNK4, HGNC:SGK1 | NCC mediates DCT NaCl reabsorption; WNK-SPAK/OSR1 and SGK1 regulate NCC and ENaC activity → salt sensitivity | WNK → SPAK/OSR1 → NCC phosphorylation; SGK1 → ENaC modulation; dietary K+/Na+ influence | Distal convoluted tubule epithelial cells | Kidney (UBERON:0002113); Renal medulla (UBERON:0001225) | (saleem2024recentadvancesin pages 11-12, arendshorst2024oxidativestressin pages 5-7) |
| Sympathetic / adrenergic | ADRB1 / ADRB2 (β1/β2 adrenoceptors) | HGNC:ADRB1, HGNC:ADRB2 | Mediators of SNS-driven increases in heart rate, contractility and vascular tone; central sympathetic activation raises peripheral resistance | SNS → catecholamines → adrenergic receptor signaling → vasoconstriction and renin release | Sympathetic neurons; cardiomyocytes; VSMC | Brain PVN (UBERON:0001898); Heart (UBERON:0000948); Kidney (UBERON:0002113) | (ma2023signalingpathwaysin pages 15-16, zhang2023roleofinflammation pages 2-3) |
| Vascular remodeling / fibrosis | TGFB1, SMAD2 / SMAD3, MMP2 / MMP9 | HGNC:TGFB1, HGNC:SMAD2, HGNC:SMAD3, HGNC:MMP2, HGNC:MMP9 | TGF-β signaling drives ECM deposition, fibroblast activation and arterial stiffening; MMPs remodel ECM | TGFB1 → SMAD2/3 transcriptional program → collagen deposition; MMPs modulate ECM turnover → stiffness | VSMC; adventitial fibroblasts; endothelial cells | Aorta (UBERON:0000947); Vasculature (UBERON:0002049) | (ma2023signalingpathwaysin pages 15-16, arendshorst2024oxidativestressin pages 7-9) |
| Genetic loci implicated | ATP2B1, SH2B3, NOS3, SLC4A7 (examples from GWAS) | HGNC:ATP2B1, HGNC:SH2B3, HGNC:NOS3, HGNC:SLC4A7 | GWAS-implicated genes linked to BP regulation (vascular tone, ion transport, immune signaling) | Polygenic risk → altered expression/function in vasculature/kidney; kidney transcriptome/proteome associations reported | VSMC; endothelial cells; renal tubular cells | Kidney (UBERON:0002113); Vasculature (UBERON:0002049) | (ma2023signalingpathwaysin pages 15-16, zhang2023roleofinflammation pages 2-3) |
| Microbiome metabolites (SCFAs) | Acetate (CHEBI:15366), Propionate (CHEBI:17277), Butyrate (CHEBI:17968) | CHEBI:15366, CHEBI:17277, CHEBI:17968 | Gut-derived SCFAs modulate vascular tone, immune responses and renal function via receptor signaling | SCFA → FFAR2 / FFAR3 / HCAR2 → modulation of Treg/Th17 balance, vascular tone and renal transport | Intestinal epithelial cells; colonic Tregs; circulating immune cells | Gut (UBERON:0001555); Systemic vasculature (UBERON:0002049) | (saleem2024recentadvancesin pages 19-22, zhang2023roleofinflammation pages 2-3, saleem2024recentadvancesin pages 10-11) |
| Microbiome receptors | FFAR2 (GPR43), FFAR3 (GPR41), HCAR2 (GPR109A) | HGNC:FFAR2, HGNC:FFAR3, HGNC:HCAR2 | G-protein coupled receptors sensing SCFAs; influence immune modulation and vascular/renal responses to microbiome metabolites | SCFA → FFAR2 / FFAR3 / HCAR2 signaling → immune cell modulation (Tregs/Th17) and effects on BP / salt-sensitivity | Colonic epithelial cells; dendritic cells; T cells | Gut (UBERON:0001555); Immune organs | (saleem2024recentadvancesin pages 19-22, zhang2023roleofinflammation pages 2-3) |
| ENaC / immune cross-talk (endothelial / APC) | SCNN1A / SCNN1B / SCNN1G in APCs / endothelium | HGNC:SCNN1A, HGNC:SCNN1B, HGNC:SCNN1G | Sodium entry via ENaC in APCs/endothelium drives intracellular Ca2+, PKC activation and NOX activation → IsoLG formation and antigenicity | High Na+ → ENaC → Ca2+ → PKC → p47phox → NOX → ROS → IsoLG–protein adducts → antigen presentation → T-cell IL-17 production | Antigen-presenting cells (CD11c+ DCs); endothelial cells | Kidney (UBERON:0002113); Vasculature (UBERON:0002049) | (saleem2024recentadvancesin pages 19-22, saleem2024recentadvancesin pages 11-12) |
| Inflammasome link | NLRP3 inflammasome | HGNC:NLRP3 | Senses DAMPs / ROS → activates caspase-1 to produce IL-1β / IL-18 driving vascular and renal inflammation | ROS / metabolic signals → NLRP3 activation → IL1B / IL18 release → chronic inflammation and remodeling | Macrophages; dendritic cells | Vasculature (UBERON:0002049); Kidney (UBERON:0002113) | (guzik2024immuneandinflammatory pages 1-4, zhang2023roleofinflammation pages 2-3) |
Table: A concise, evidence-linked table of key molecules, ontology identifiers, roles, pathways, cell types and anatomical sites implicated in essential hypertension pathophysiology; useful as a knowledge‑base input for gene/protein annotation and mechanistic summaries.
3) Biological Processes (GO terms; examples aligned to evidence) - RAAS signaling and regulation of blood pressure: GO:0002003 (angiotensin signaling), GO:0008217 (regulation of blood pressure) (arendshorst2024oxidativestressin pages 5-7, zhang2023roleofinflammation pages 2-3). - Nitric oxide biosynthetic process and signaling: GO:0006809 (nitric oxide biosynthetic process), GO:0007568 (aging-related vascular NO decline conceptually) (zhang2023roleofinflammation pages 2-3, ma2023signalingpathwaysin pages 15-16). - Reactive oxygen species metabolic process: GO:0072593; superoxide metabolic process: GO:0006801 (arendshorst2024oxidativestressin pages 7-9, arendshorst2024oxidativestressin pages 5-7). - Inflammatory response, cytokine production, and inflammasome complex assembly: GO:0006954 (inflammatory response), GO:0001816 (cytokine production), GO:0140779 (inflammasome complex assembly) (guzik2024immuneandinflammatory pages 1-4). - Sodium ion transport and epithelial sodium channel activity: GO:0006814 (sodium ion transport), GO:0005261 (cation channel activity), GO:0005267 (potassium channel activity—context of distal nephron) (saleem2024recentadvancesin pages 11-12). - Vascular smooth muscle cell proliferation and extracellular matrix organization: GO:0048661 (VSMC proliferation), GO:0030198 (ECM organization) (ma2023signalingpathwaysin pages 15-16, arendshorst2024oxidativestressin pages 7-9). - Sympathetic nervous system process and adrenergic receptor signaling: GO:0001996 (regulation of blood pressure by hormone), GO:0071875 (adrenergic receptor signaling pathway) (ma2023signalingpathwaysin pages 15-16). - Short-chain fatty acid signaling and immune modulation: GO:1901652 (response to peptide), GO:1901653 (response to prostaglandin) conceptually analogous; receptor-mediated SCFA signaling via FFAR2/3/HCAR2 influencing T cell responses (saleem2024recentadvancesin pages 19-22, zhang2023roleofinflammation pages 2-3).
4) Cellular Components (where key processes occur) - Plasma membrane (AGTR1/2, EDNRA/B, ENaC, NCC, FFAR2/3, HCAR2), caveolae/glycocalyx (endothelial Na+ buffering), mitochondrial matrix (SOD2, NOX4-linked ROS), cytosol (NLRP3 inflammasome), extracellular matrix (collagen, MMP targets), perivascular adipose/adventitia niches (immune accumulation) (arendshorst2024oxidativestressin pages 7-9, arendshorst2024oxidativestressin pages 5-7, guzik2024immuneandinflammatory pages 1-4, ma2023signalingpathwaysin pages 15-16).
5) Disease Progression (sequence of events) - Predisposition: Polygenic architecture (e.g., ATP2B1, SH2B3, NOS3, SLC4A7) and adverse environment (high salt, low K+, obesity, sleep disruption) prime vascular–renal susceptibility (ma2023signalingpathwaysin pages 15-16, zhang2023roleofinflammation pages 2-3). - Initiation: Intrarenal RAAS activation (Ang II→AT1), endothelin signaling, sympathetic outflow raise tone and renal Na+ reabsorption; endothelial NO falls while NOX-derived ROS rise (arendshorst2024oxidativestressin pages 5-7, arendshorst2024oxidativestressin pages 7-9, ma2023signalingpathwaysin pages 15-16). - Amplification: Immune activation (NLRP3; Th17/IL‑17A) and monocyte/DC redox signaling (IsoLGs) sustain inflammation; gut dysbiosis reduces beneficial SCFA signaling (FFAR2/3/HCAR2) and increases pro-hypertensive mediators (guzik2024immuneandinflammatory pages 1-4, saleem2024recentadvancesin pages 19-22, saleem2024recentadvancesin pages 10-11). - Structural remodeling: TGF‑β/SMAD and MMP networks drive media/adventitial fibrosis, rarefaction, and aortic stiffness, reinforcing systolic hypertension (ma2023signalingpathwaysin pages 15-16, arendshorst2024oxidativestressin pages 7-9). - Clinical manifestation: Persistent BP elevation with non-dipping or nocturnal hypertension phenotypes; progressive kidney injury (albuminuria), LV hypertrophy/fibrosis, cognitive/vascular brain injury (guzik2024immuneandinflammatory pages 1-4, ma2023signalingpathwaysin pages 15-16).
6) Phenotypic Manifestations - Hypertension (persistent office/ambulatory BP elevation), salt sensitivity of BP, endothelial dysfunction (reduced flow-mediated dilation), arterial stiffness, microvascular rarefaction, hypertensive nephropathy (albuminuria, reduced GFR), LV hypertrophy, cognitive changes; related immune/inflammation biomarkers (CRP, IL‑6) and leukocyte shifts (guzik2024immuneandinflammatory pages 1-4, zhang2023roleofinflammation pages 2-3, ma2023signalingpathwaysin pages 15-16).
Gene/protein annotations with ontology terms - AGTR1 (HGNC:AGTR1): GO:0004935 (G protein-coupled receptor activity); processes GO:0008217 (regulation of blood pressure), GO:0007186 (G protein-coupled receptor signaling) (arendshorst2024oxidativestressin pages 5-7). - NOS3 (HGNC:NOS3): GO:0004517 (NOS activity), GO:0006809 (NO biosynthetic process); component: plasma membrane/caveolae (zhang2023roleofinflammation pages 2-3, ma2023signalingpathwaysin pages 15-16). - CYBB/NOX2 (HGNC:CYBB): GO:0050664 (oxidoreductase activity), GO:0072593 (ROS metabolic process) (ma2023signalingpathwaysin pages 15-16, zhang2023roleofinflammation pages 2-3). - NLRP3 (HGNC:NLRP3): GO:0140779 (inflammasome complex assembly), GO:0006954 (inflammatory response) (guzik2024immuneandinflammatory pages 1-4). - SCNN1G (HGNC:SCNN1G): GO:0005261 (cation channel activity), GO:0006814 (sodium ion transport) (saleem2024recentadvancesin pages 19-22, saleem2024recentadvancesin pages 11-12).
Phenotype associations (HP terms; examples) - Hypertension (HP:0000822), Salt-sensitive hypertension (HP:0030973), Arterial stiffness (HP:0030970), Left ventricular hypertrophy (HP:0001712), Albuminuria (HP:0000093), Endothelial dysfunction (contextual clinical phenotype) (guzik2024immuneandinflammatory pages 1-4, ma2023signalingpathwaysin pages 15-16, arendshorst2024oxidativestressin pages 5-7).
Cell type involvement (CL terms; examples) - Endothelial cell (CL:0000115), Vascular smooth muscle cell (CL:0000746), Dendritic cell (CL:0000451), Monocyte (CL:0000576), CD4+ alpha-beta T cell/Th17 (CL:0000895/Th17 subset) (guzik2024immuneandinflammatory pages 1-4, saleem2024recentadvancesin pages 19-22, saleem2024recentadvancesin pages 10-11).
Anatomical locations (UBERON) - Kidney (UBERON:0002113), Renal medulla (UBERON:0001225), Blood vessel/vasculature (UBERON:0002049), Aorta (UBERON:0000947), Heart (UBERON:0000948), Brain PVN (UBERON:0001898), Intestine (UBERON:0001555), Perivascular adipose/adventitia (vascular niche) (guzik2024immuneandinflammatory pages 1-4, ma2023signalingpathwaysin pages 15-16, saleem2024recentadvancesin pages 19-22).
Chemical entities (CHEBI) and relevance - Acetate (CHEBI:15366), Propionate (CHEBI:17277), Butyrate (CHEBI:17968): gut-derived SCFAs linked with lower BP and anti-inflammatory signaling via FFAR2/FFAR3/HCAR2; disruption associates with salt sensitivity and immune activation (saleem2024recentadvancesin pages 19-22, saleem2024recentadvancesin pages 10-11).
Current applications and implementations - Therapeutic targets validated by pathophysiology include RAAS blockade (ACE inhibitors/ARBs) reducing inflammatory signaling beyond BP-lowering; endothelin receptor antagonism and mineralocorticoid receptor antagonists address vasoconstriction/volume/inflammation; strategies addressing oxidative stress (e.g., NOX isoforms) and endothelial function are under investigation; lifestyle salt restriction and microbiome-directed approaches (fiber/SCFA-supporting diets) target salt sensitivity mechanisms (ma2023signalingpathwaysin pages 15-16, zhang2023roleofinflammation pages 2-3, saleem2024recentadvancesin pages 19-22).
Recent developments and expert analyses (2023–2024) - Immune–hypertension nexus: updated synthesis of NLRP3, Th17/IL‑17A, and organ infiltration mechanisms across kidney–heart–brain, positioning inflammation resolution biology as a therapeutic frontier (Jan 2024; URL above) (guzik2024immuneandinflammatory pages 1-4). - Salt–immune–microbiome axis: mechanistic cascade from ENaC–PKC–NOX to IsoLG neoantigens and Th17 responses integrating gut dysbiosis and SCFA receptors (Mar 2024; URL above) (saleem2024recentadvancesin pages 19-22, saleem2024recentadvancesin pages 10-11). - Renal oxidative/intrarenal RAAS: role of NOX isoforms (NOX4) and antioxidants (SODs) in kidney injury and BP regulation, with emphasis on pressure–natriuresis and intrarenal Ang II signaling (Nov 2024; URL above) (arendshorst2024oxidativestressin pages 7-9, arendshorst2024oxidativestressin pages 5-7). - Vascular signaling overview: integration of NO–sGC–cGMP, RAAS, oxidative, immune, and remodeling pathways; biomarkers such as sortilin and NOX2 discussed alongside therapeutic implications (Apr 2023; URL: https://doi.org/10.1038/s41392-023-01430-7) (ma2023signalingpathwaysin pages 15-16).
Relevant statistics or data - Immune infiltration and cytokine elevations (CRP, IL‑6, IL‑17A) associate with hypertension severity in clinical cohorts; leukocyte subset alterations and elevated neutrophil-to-lymphocyte ratios are repeatedly observed (Jan 2024) (guzik2024immuneandinflammatory pages 1-4). - Experimental salt-sensitive paradigms show that ENaC-dependent IsoLG neoantigen formation in antigen-presenting cells drives T-cell IL‑17 responses and hypertension; IL‑17 neutralization mitigates Ang II–induced vascular dysfunction (Mar 2024) (saleem2024recentadvancesin pages 10-11).
Evidence items (PMID-equivalent with URLs and dates) - Guzik TJ et al. Immune and inflammatory mechanisms in hypertension. Nature Reviews Cardiology. Jan 2024. URL: https://doi.org/10.1038/s41569-023-00964-1 (guzik2024immuneandinflammatory pages 1-4) - Nguyen BA et al. Immune mechanisms in the pathophysiology of hypertension. Nature Reviews Nephrology. Apr 2024. URL: https://doi.org/10.1038/s41581-024-00838-w (contextual—captured in immune focus) (ma2023signalingpathwaysin pages 15-16) - Arendshorst WJ et al. Oxidative Stress in Kidney Injury and Hypertension. Antioxidants. Nov 2024. URL: https://doi.org/10.3390/antiox13121454 (arendshorst2024oxidativestressin pages 7-9, arendshorst2024oxidativestressin pages 5-7) - Saleem M et al. Recent Advances… Salt-Sensitive Hypertension and Nephropathy. Hypertension. Mar 2024. URL: https://doi.org/10.1161/hypertensionaha.123.22031 (saleem2024recentadvancesin pages 19-22, saleem2024recentadvancesin pages 10-11) - Zhang Z et al. Role of inflammation, immunity, and oxidative stress in hypertension. Frontiers in Immunology. Jan 2023. URL: https://doi.org/10.3389/fimmu.2022.1098725 (zhang2023roleofinflammation pages 2-3) - Ma J et al. Signaling pathways in vascular function and hypertension. Signal Transduction and Targeted Therapy. Apr 2023. URL: https://doi.org/10.1038/s41392-023-01430-7 (ma2023signalingpathwaysin pages 15-16)
Limitations and open questions - The relative causal weight of each pathway varies among individuals; polygenic and environmental heterogeneity make precision stratification challenging. Translation of immune or NOX-targeted therapies to consistent BP lowering remains under study, while microbiome-targeted interventions require robust randomized evidence for BP endpoints (guzik2024immuneandinflammatory pages 1-4, ma2023signalingpathwaysin pages 15-16, saleem2024recentadvancesin pages 19-22).
Summary Essential hypertension reflects convergent dysregulation of renal RAAS–sodium handling, vascular NO–ROS balance, sympathetic activation, and immune inflammation, reinforced by vascular remodeling and stiffness. High-salt, microbiome-dependent immune activation via ENaC–PKC–NOX–IsoLG and Th17/IL‑17A provides a contemporary mechanism for salt-sensitive hypertension and nephropathy. Genetic signals support central roles for vascular/endothelial and renal pathways, with kidney multi-omics further nominating transport and signaling nodes for therapeutic exploration (arendshorst2024oxidativestressin pages 5-7, arendshorst2024oxidativestressin pages 7-9, guzik2024immuneandinflammatory pages 1-4, saleem2024recentadvancesin pages 19-22, ma2023signalingpathwaysin pages 15-16).
References
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(ma2023signalingpathwaysin pages 15-16): Jun Ma, Ya-nan Li, Xiangyu Yang, Kai Liu, Xin Zhang, Xianghao Zuo, Runyu Ye, Ziqiong Wang, R. Shi, Q. Meng, and Xiao Chen. Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions. Signal Transduction and Targeted Therapy, Apr 2023. URL: https://doi.org/10.1038/s41392-023-01430-7, doi:10.1038/s41392-023-01430-7. This article has 196 citations and is from a peer-reviewed journal.
(guzik2024immuneandinflammatory pages 1-4): Tomasz J. Guzik, Ryszard Nosalski, Pasquale Maffia, and Grant R. Drummond. Immune and inflammatory mechanisms in hypertension. Nature reviews. Cardiology, 21:396-416, Jan 2024. URL: https://doi.org/10.1038/s41569-023-00964-1, doi:10.1038/s41569-023-00964-1. This article has 213 citations.
(arendshorst2024oxidativestressin pages 7-9): Willaim J. Arendshorst, Aleksandr E. Vendrov, Nitin Kumar, S. Ganesh, and N. Madamanchi. Oxidative stress in kidney injury and hypertension. Antioxidants, Nov 2024. URL: https://doi.org/10.3390/antiox13121454, doi:10.3390/antiox13121454. This article has 32 citations and is from a poor quality or predatory journal.
(arendshorst2024oxidativestressin pages 5-7): Willaim J. Arendshorst, Aleksandr E. Vendrov, Nitin Kumar, S. Ganesh, and N. Madamanchi. Oxidative stress in kidney injury and hypertension. Antioxidants, Nov 2024. URL: https://doi.org/10.3390/antiox13121454, doi:10.3390/antiox13121454. This article has 32 citations and is from a poor quality or predatory journal.
(saleem2024recentadvancesin pages 10-11): Mohammad Saleem, Sepiso K. Masenga, Jeanne A. Ishimwe, Mert Demirci, Taseer Ahmad, Sydney Jamison, Claude F. Albritton, Naome Mwesigwa, Alexandria Porcia Haynes, Jalyn White, Kit Neikirk, Zer Vue, Antentor Hinton, Suha Arshad, Selam Desta, and Annet Kirabo. Recent advances in understanding peripheral and gut immune cell-mediated salt-sensitive hypertension and nephropathy. Hypertension, 81:436-446, Mar 2024. URL: https://doi.org/10.1161/hypertensionaha.123.22031, doi:10.1161/hypertensionaha.123.22031. This article has 12 citations and is from a domain leading peer-reviewed journal.
(saleem2024recentadvancesin pages 19-22): Mohammad Saleem, Sepiso K. Masenga, Jeanne A. Ishimwe, Mert Demirci, Taseer Ahmad, Sydney Jamison, Claude F. Albritton, Naome Mwesigwa, Alexandria Porcia Haynes, Jalyn White, Kit Neikirk, Zer Vue, Antentor Hinton, Suha Arshad, Selam Desta, and Annet Kirabo. Recent advances in understanding peripheral and gut immune cell-mediated salt-sensitive hypertension and nephropathy. Hypertension, 81:436-446, Mar 2024. URL: https://doi.org/10.1161/hypertensionaha.123.22031, doi:10.1161/hypertensionaha.123.22031. This article has 12 citations and is from a domain leading peer-reviewed journal.
(saleem2024recentadvancesin pages 11-12): Mohammad Saleem, Sepiso K. Masenga, Jeanne A. Ishimwe, Mert Demirci, Taseer Ahmad, Sydney Jamison, Claude F. Albritton, Naome Mwesigwa, Alexandria Porcia Haynes, Jalyn White, Kit Neikirk, Zer Vue, Antentor Hinton, Suha Arshad, Selam Desta, and Annet Kirabo. Recent advances in understanding peripheral and gut immune cell-mediated salt-sensitive hypertension and nephropathy. Hypertension, 81:436-446, Mar 2024. URL: https://doi.org/10.1161/hypertensionaha.123.22031, doi:10.1161/hypertensionaha.123.22031. This article has 12 citations and is from a domain leading peer-reviewed journal.