This is a mechanism module, not a specific disease. It is a pathological structure-formation ("Xogenesis") module. Xogenesis anchor: the terminal output is an atheroma / atherosclerotic plaque, an OGMS:0000078 pathological anatomical structure produced by an OGMS:0000081 pathological derivation (a new intimal lesion); process genus OGMS:0000061 pathological bodily process; site UBERON:0001637 artery. MPATH represents the lesion as MPATH:28 (atherosclerosis) but has no distinct "atheroma"/"atherosclerotic plaque" continuant class, a noted OBO gap. SNOMED "Morphologically abnormal structure" (49755003) is used only as an external census/gap guide and is not bound here. Disorder entries reference individual nodes via conforms_to (for example, "atherogenesis#Smooth Muscle Cell Switching and Fibrofatty Plaque Formation"). The module defines the expected pathophysiology structure; conforming nodes in disorder files should include the corresponding cell types, biological processes, and causal edges, specialized to their disease context. A pathophysiology branch is within scope when it explicitly represents formation of an arterial-intimal atheroma through (1) retention of apoB-containing lipoprotein in the arterial intima, with oxidative or enzymatic modification as a possible specialization, (2) monocyte/macrophage foam-cell biology, and (3) vascular-smooth-muscle-cell and extracellular-matrix assembly of a fibrofatty plaque. This core three-stage chain is the operational necessary-and-sufficient curation boundary for module conformance; it is a prose guardrail, not a formal grouping criterion. Advanced necrotic core/fibrous cap, rupture or erosion with thrombosis, stenosis, and ischemia may be mapped when the disorder explicitly represents those later stages, but none is required and none is sufficient alone. Exclude hyperlipidemia or vascular risk without an explicit arterial plaque-forming branch, foam cells outside arterial atheroma, nonatherosclerotic stenosis, dissection or thrombosis, and terminal ischemia without modeled plaque formation. Because conformance is node-level, an explicit atherosclerotic branch of a mixed-etiology disorder may qualify without asserting that every disease mechanism is atherogenic. Familial hypercholesterolemia substitutes a high LDL/apoB burden at the retention trigger; diabetic atherosclerosis substitutes hyperglycemia and advanced glycation end-products; the terminal rupture/thrombosis node feeds the thrombogenesis module. Mechanism nodes bind GO, CL, and UBERON terms where appropriate and do not use chemical (CHEBI) or disease (MONDO) term bindings, except in the treatments block where the therapeutic agent carries an ontology identifier per the treatment schema.
Endothelial Dysfunction and Subendothelial LDL Retention
trigger
The proximal trigger of atherogenesis. Endothelial dysfunction - from disturbed flow, hypercholesterolemia, hypertension, smoking, or hyperglycemia - increases arterial-wall permeability and alters the subendothelial matrix, permitting infiltration and retention of apoB-containing lipoproteins (LDL) in the intima. Retained LDL is oxidatively and enzymatically modified, becoming a pro-inflammatory stimulus. This subendothelial lipoprotein retention is the critical initiating event of the plaque; the disease-specific driver differs but the retained-LDL trigger is shared.
Downstream
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Monocyte Recruitment and Macrophage Foam Cell Formation
Show evidence (2 references)
"infiltration and retention of apoB containing lipoproteins in the artery wall is a critical initiating event that sparks an inflammatory response and promotes the development of atherosclerosis."
Identifies subendothelial retention of apoB-containing lipoproteins as the critical initiating event of atherosclerosis, the trigger of this module. Evidence source is OTHER because this is an authoritative review chapter.
"Endothelial cell dysfunction in the walls of blood vessels results in an increase in vascular permeability, alteration of the components of the extracellular matrix, and retention of LDL in the sub-endothelial space, thereby accelerating plaque formation."
Links endothelial dysfunction to increased permeability and subendothelial LDL retention accelerating plaque formation, the trigger of this module. Evidence source is OTHER because this is a review.
Advanced Atheroma with Necrotic Core and Fibrous Cap
effector
Continued lipid accumulation, foam-cell death, and matrix remodeling enlarge the plaque into an advanced atheroma with a soft necrotic lipid core walled off by a fibrous cap. Local microenvironmental changes - neovascularization from the vasa vasorum, intraplaque hemorrhage, and necrotic-core expansion - promote the transition from a stable to an unstable (vulnerable) atheroma. This is the mature pathological structure the module produces.
Downstream
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Plaque Rupture, Thrombosis, and Ischemic Events
Show evidence (1 reference)
"the local arterial microenvironment of a stable atheroma promotes destabilizing conditions that result in the transition to an unstable atheroma."
Establishes the advanced atheroma and its microenvironment-driven transition from stable to unstable plaque, the effector structure of this module. Evidence source is OTHER because this is a histopathology review.
Plaque Rupture, Thrombosis, and Ischemic Events
consequence
The clinical end state of the module. Fibrous-cap rupture (or endothelial erosion) of an unstable atheroma exposes the thrombogenic necrotic core and subendothelial matrix to flowing blood, triggering luminal thrombosis (see the thrombogenesis module). The resulting thrombotic vascular occlusion causes acute ischemic events - acute coronary syndrome, myocardial infarction, and ischemic stroke - the consequence of the conserved atherogenesis chain.
Show evidence (3 references)
"There are several rupture-associated phenotypes causing thrombotic vascular occlusion including simple fibrous cap rupture of an atheroma, fibrous cap rupture at site of previous rupture-and-repair of an atheroma, and nodular calcification with rupture."
Documents fibrous-cap rupture of the atheroma causing thrombotic vascular occlusion, the consequence that links atherogenesis to acute ischemic events. Evidence source is OTHER because this is a histopathology review.
"Destabilization is characterized by several different plaque phenotypes that cause major clinical events such as acute coronary syndrome and cerebrovascular strokes."
Establishes acute coronary syndrome and stroke as the major clinical events caused by atheroma destabilization, the consequence of this module. Evidence source is OTHER because this is a review.
"Endothelial erosion without rupture has more recently been shown to be a common phenotype to promote thrombosis as well."
Directly supports endothelial erosion as a thrombosis-promoting alternative to fibrous-cap rupture in the consequence node. Evidence source is OTHER because this is a histopathology review.
LDL-Lowering Therapy (Statin)
Platform:
Small molecule
Statins (HMG-CoA reductase inhibitors, e.g., atorvastatin) lower circulating LDL cholesterol, the apoB-containing lipoprotein retained in the artery wall. By reducing the retained-LDL substrate that initiates and fuels the plaque, LDL-lowering therapy slows atheroma formation and progression and reduces atherosclerotic cardiovascular events. Represents the atherogenesis drug-target design pattern for conforming disorders, acting on the LDL-retention trigger rather than on the established plaque.
Evidence: 2