title: The significance of programmed cell death or apoptosis and matrix vesicles in atherogenesis.
abstract: Programmed cell death or its current synonym, apoptosis, is considered a genetically controlled biological process of cell deletion complementary to cell replication. Apoptosis is most likely a self-regulatory mechanism whereby a genetically determined biochemical pathway to death is initiated in cells sustaining irreparable damage particularly of DNA. Initiating factors in each instance need to be established. Identified in arteries, apoptosis correlates with the localization and severity of atherosclerosis. Granulovesicular disintegration of vascular smooth muscle cells leads to abundant vesicular debris mostly in the intima and increasing with age and hypertension and such matrix vesicle production is a major pathogenetic feature of atherosclerosis. The abundant debris produced accumulates lipid and minerals as usually occurs in non-phagocytosed cell debris. Similar vesiculation in erythrocytes under haemodynamic stress supports the contention that vascular cells under haemodynamic biomechanical stresses in spontaneous and experimental atherosclerosis degenerate due to depletion of cytoplasm, DNA fragmentation and oxidative damage with some cells inevitably undergoing terminal apoptosis. Evaluation of apoptosis must take into account the concomitant changes in the whole vessel wall and its matrix. Currently generalizations about therapeutic or pathogenetic roles for apoptosis in any disease are speculative and unwarranted.
authors.affiliation: Department of Pathology, Wellington School of Medicine, Wellington South, New Zealand. wstehbens@wnmeds.ac.nz
authors.forename: W E
authors.initials: WE
authors.lastname: Stehbens
mesh_terms: D000818:Animals; D017209:Apoptosis; D001161:Arteriosclerosis / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D006439:Hemodynamics; D006801:Humans; D008854:Microscopy, Electron; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000648:ultrastructure