Development of Atherosclerosis
Endothelial cell injury
The vascular endothelium consists of a single layer of cells with cell to cell attachments, which normally protects the subendothelial layers form interacting with blood cells and other blood components. Elevated LDLs, immune mechanisms and mechanical stress associated with hypertension are risk factors.
2. Migration of Inflammatory Cells
Early in the development of atherosclerotic lesions, endothelial cells begin to express selective adhesion molecules that bind monocytes and other inflammatory cells that initiate the atherosclerotic lesion formation.
After monocytes adhere to the endothelium, they migrate between the endothelial cells to localize in the intima, transform into macrophages, and engulf lipoproteins (largely LDLs)
3. Lipid Accumulation and Smooth Muscle Cell Proliferation
All through the recruitment of monocytes, their differentiation into macrophages and subsequent ingestion of lipids, and their ultimate transformation into foam cells is protective in that it removes excess lipids from the circulation, but progressive accumulation eventually leads to lesion progression.
Activated macrophages release toxic oxygen species that oxidize LDLs
macrophages ingest the oxidized LDLs to become foam cells.
They also produce growth factors that contribute tot he migration and proliferation of smooth muscle cells and the elaboration of extracellular matrix.
4. Plaque Structure
Atherosclerotic plaques consist of an aggregation of smooth muscle cells, macrophages and other leukocytes, extracellular matrix, including collagen and elastic fibers, intracellular and extracellular lipids.
Typically, the superficial fibrous cap is composed of smooth muscle and dense extracellular matrix.
Immediately beneath and to the side of the fibrous cap is a cellular area (the shoulder) consisting of macrophages, smooth muscle cells, and lymphocytes.
Below the fibrous cap is a central core of lipid-laden foam cells and fatty debris.
Rupture, ulceration or erosion of an unstable or vulnerable fibrous cap may lead to hemorrhage into the plaque or thrombocytic occlusion of the vessel lumen.
Sites of severe atherosclerosis in order of frequency
Abdominal aorta and iliac arteries
Proximal coronary arteries
Thoracic aorta, femoral and popliteal arteries
Internal carotid arteries
Vertebral, basilar and middle cerebral arteries
Martin, Glenn and Porth, Carol, Mattson. 2009. Pathophysiology Concepts of Altered Health States. 8th ed. Lippincott Williams and Wilkins. Philadelphia