Genetic instability and atherosclerosis: can somatic mutations account for the development of cardiovascular diseases?

Several observations suggest that cancer and atherosclerosis may entail fundamentally common biological mechanisms. The accumulation of lipids and the proliferation of smooth muscle cells (SMCs) are the main histological features of sclerotic plaque formation. The most prominent theory concerning the pathophysiological mechanisms of atherosclerotic plaque formation is the "inflammatory response to injury" hypothesis, which states that SMC proliferation 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 disease. In accordance with these findings, the "monoclonal" hypothesis of atherosclerosis has been suggested. This hypothesis proposes that atherosclerosis begins as a mutation or viral infection, transforming a single, isolated smooth muscle cell into the progenitor of a proliferative clone, as seen in carcinogenesis. Studies of DNA damage in atherosclerotic tissues are lacking. Biological evidence for the hypothesis that cancer and atherosclerosis may share pathological mechanisms is discussed, emphasizing the need to perform studies investigating the involvement of somatic mutations in heart diseases. Copyright 2000 Wiley-Liss, Inc.