Biologic effect and molecular regulation of vascular apoptosis in atherosclerosis

Abstract

Apoptosis, a form of genetically programmed cell death, plays a key role in regulation of cellularity of the arterial wall. During atherogenesis, deregulated apoptosis may cause abnormalities of arterial morphogenesis, wall structural stability, and metabolisms. Many biophysiologic and biochemical factors, including mechanical forces, reactive oxygen and nitrogen species, cytokines, growth factors, oxidized lipoproteins, etc. may influence apoptosis of vascular cells. The Fas/Fas ligand/caspase death-signaling pathway, Bcl-2 protein family/mitochondria, the tumor suppressive gene p53, and the proto-oncogene c-myc may be activated in atherosclerotic lesions and mediate vascular apoptosis during the development of atherosclerosis. Abnormal expression and dysfunction of these apoptosis-regulating genes may attenuate or accelerate vascular cell apoptosis and affect the integrity and stability of plaques. Clarification of the molecular mechanism that regulates apoptosis may help design a new strategy for treatment of atherosclerosis and its major complication, the acute vascular syndromes.