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Atherosclerosis
Atherosclerosis
For medical students2 min readUpdated 2026-10-10
Atherosclerosis is a pathological process driven by a combination of hyperlipidemia (or dyslipoproteinemia) and vascular endothelial injury. The disease begins with microscopic alterations in the arterial intima and progressively advances through stages of lipoidosis and liposclerosis, ultimately resulting in the formation of a fibrous plaque.
Main targetArterial intima (inner layer)
Disease onsetPre-lipid stage is visible only via electron microscopy
Pathogenetic basisHyperlipidemia and dyslipoproteinemia
Myasnikov's triadHyperlipidemia, excess catecholamines, and vasomotor reactions
Pathogenesis: Vascular Wall Injury
The foundation for atherosclerotic plaque formation requires the simultaneous presence of hyperlipidemia and endothelial injury. Notably, the vascular intima is most often damaged not by a single isolated trigger, but by the combined impact of multiple aggressive factors.
Primary factors damaging the endothelial lining include:
Circulating immune complexes and other immune system components.
Direct effects of various toxins and viruses.
Hemodynamic disturbances: arterial hypertension, vascular spasms or paresis, and blood rheology disorders.
Major Theories of Pathogenesis
Modern pathology recognizes several theories regarding the primary trigger of the disease. Most clinically validated concepts are based on the premise that the process initiates from a combination of blood property alterations and injury to the arterial intima.
Infiltration Theory (N.N. Anichkov, S.S. Khalatov). A historically significant concept stating that exogenous hypercholesterolemia and hyperlipidemia are the primary causes. Excess blood lipids penetrate and infiltrate the vascular wall.
Neuro-Metabolic Theory (A.L. Myasnikov). Emphasizes repeated stress and psycho-emotional strain, which disrupt the neuroendocrine regulation of protein and lipid metabolism, inducing vasomotor disorders. This forms a pathological triad: hyperlipidemia + hypercatecholaminemia + vasomotor reactions, ultimately injuring the endothelium.
Immunological Theory (A.N. Klimov, V.A. Nagornev). Views atherosclerosis as a form of immune-mediated inflammation. Evidence includes autoimmune complexes within the vessel wall, infiltration by immunocompetent cells, and accelerated disease progression in organ transplant recipients on immunosuppressive therapy.
Receptor Theory (Goldstein, Brown). Explains dietary and hereditary hyperlipidemias through defects in specific lipoprotein receptors.
Monoclonal (Neoplastic) Theory. Proposes that atherogenesis is driven by cell-cycle gene mutations leading to the proliferation of vascular smooth muscle cells, which subsequently initiate the sclerotic process.
Thrombogenic Theory (Duguid). Based on the formation of flat mural thrombi in arteries with their subsequent organization (replacement by connective tissue).
Viral Theory. Confirmed primarily in experimental settings, studying the role of viral agents in vascular wall injury.
Morphogenetic Stages of Atherosclerosis
The pathogenesis and morphogenesis of atherosclerosis comprise strictly sequential stages that reflect the dynamics within the plaque:
Pre-lipid stage. Intimal injury at this stage stems from blood composition changes. The vessel appears grossly unaltered, as initial damage is visible only under an electron microscope.
Lipoidosis stage. Characterized by the onset of visible lipid accumulation. Specific lipid spots and streaks form in the arterial intima.
Liposclerosis stage. Active proliferation of connective tissue surrounds the lipid deposits, forming a fibrous plaque.
To remember the morphogenetic stages, use the sequence: Pre-lipid, Lipoidosis, Liposclerosis, Complicated lesions.
Frequently asked questions
What is the role of receptors in the development of hyperlipidemia according to Goldstein and Brown?
According to Goldstein and Brown, defects in lipoprotein receptors underlie hereditary forms and dietary hyperlipidemias. LDL receptors on cell membranes are the critical pathogenetic link. In hereditary disorders, LDL receptor deficiency is primary, driven by mutations in genes encoding LDL receptor synthesis and function. In secondary/dietary hyperlipidemias, receptor deficiency is secondary. Excess LDL, VLDL, and modified apo-β-lipoproteins block cell membrane LDL receptors, suppressing regulated lipoprotein metabolism. Under blocked normal receptors, macrophage system cells activate, taking up excess lipids via scavenger receptors in an unregulated manner.
What macroscopic changes does the aorta undergo in the terminal stage of atherosclerosis?
In the complicated lesions stage of atherosclerosis, fibrous plaque changes include:
Ulceration;
Calcification;
Thrombosis;
Intraplaque hemorrhage.
Clinico-anatomically, these modified fibrous plaques lead to arterial stenosis, thrombosis, and occlusion. In atherosclerotic aneurysms, arterial wall dissection and rupture with massive hemorrhage may occur.
Which layer of the artery is damaged first in atherosclerosis?
The pathological process always begins with injury to the intima (inner layer) of arteries driven by alterations in blood composition.
What is the core premise of Anichkov's infiltration theory?
It posits that the primary cause of the disease is exogenous hypercholesterolemia, causing lipids to infiltrate the vascular wall.
Can initial manifestations of atherosclerosis be seen under a standard light microscope?
No, the earliest (pre-lipid) stage features microscopic intimal lesions visible exclusively via electron microscopy.
What role do smooth muscle cells play according to the monoclonal theory?
According to this theory, cell-cycle gene mutations trigger the active proliferation of vascular smooth muscle cells, initiating the sclerotic process.
Go deeper
Detailed analysis of atherosclerosis pathogenesis (diagrams and mechanisms)
Morphological characteristics of lipoidosis and liposclerosis stages
Types of complicated lesions: ulceration, calcification, thrombosis
Role of smooth muscle cells in atherogenesis
Immune inflammation in the vascular wall during atherosclerosis