Genetic instability and atherosclerosis: Can somatic mutations account forthe development of cardiovascular diseases?

Several observations suggest that cancer and athero sclerosis may entail fu ndamentally common biological mechanisms. The accumulation of lipids and th e proliferation of smooth muscle cells (SMCs) are the main histological fea tures of sclerotic plaque formation. The most prominent theory concerning t he pathophysiological mechanisms of atherosclerotic plaque formation is the "inflammatory response to injury" hypothesis, which states that SMC prolif eration is an inflammation-fibroproliferative reaction to different insults to the artery wall. However, recent evidence suggests that alterations at the DNA level may contribute significantly to the development of the diseas e. In accordance with these Findings, the "monoclonal" hypothesis of athero sclerosis has been suggested. This hypothesis proposes that atherosclerosis begins as a mutation or viral infection, transforming a single, isolated s mooth muscle cell into the progenitor of a proliferative clone, as seen in carcinogenesis. Studies of DNA damage in atherosclerotic tissues are lackin g. Biological evidence for the hypothesis that cancer and atherosclerosis m ay share pathological mechanisms is discussed, emphasizing the need to perf orm studies investigating the involvement of somatic mutations in heart dis eases. (C) 2000 Wiley-Liss, Inc.