Cell biology of atherosclerosis.
FATTY STREAKS: The precursors of atherosclerotic plaques, fatty streaks, are subendothelial aggregations of lipid-filled macrophages which appear in human arteries within the first decade of life. Some fatty streaks disappear while others progress to fibrous plaques by about the fourth decade.
The major cells comprising plaques are phenotypically modified, smooth-muscle, monocyte-derived, macrophages and T lymphocytes. The monocyte/macrophages and T lymphocytes are chemoattracted into the vessel wall by substances such as oxidized lipoprotein following their adhesion to a dysfunctional endothelium (caused for example by hyperlipidaemia, hypertension or diabetes). The macrophages and T lymphocytes produce specific matrix-degrading enzymes that initiate smooth muscle phenotypic change to a state in which they are responsive to a vast array of mitogens released by cells within the artery wall and by degranulating platelets. Cytokines also released are mediators of an immune response. These processes result in the formation of a thick fibrous cap of proliferated, phenotypically modified, smooth muscle cells and the extracellular matrix that they have produced, overlying a laterally placed cellular region of macrophages, T lymphocytes and smooth muscle cells and a central core of cell debris and cholesterol which has formed from necrotic, lipid-filled macrophages and smooth muscle cells. THROMBI: Ulceration and splitting of the fibrous cap exposes the highly thrombogenic necrotic core to flowing blood, resulting in thrombi which can travel distally to occlude smaller vessels and produce (dependent on the site of the plaque) myocardial infarction, stroke or gangrene of the extremities.
Campbell
J H
JH
Department of Anatomical Sciences, University of Queensland, Brisbane, Australia.
Campbell
G R
GR
D001161:Arteriosclerosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D002448:Cell Adhesion; D016207:Cytokines / Q000502:physiology; D006801:Humans; D009389:Neovascularization, Pathologic
D016207:Cytokines