Mutagenesis and cardiovascular diseases Molecular mechanisms, risk factors, and protective factors.

Although no generalization can be made, it is of interest that cancer, cardiovascular diseases, and other chronic conditions often share common risk factors and common protective factors as well as common pathogenetic determinants, such as DNA damage, oxidative stress, and chronic inflammation. Atherosclerosis is the most important cause of vascular forms representing the major cause of death in the population of many geographical areas. A great deal of studies support the "response-to-injury" theory. A variety of experimental and epidemiological findings are also in favor of the somatic mutation theory, which maintains that the earliest event in the atherogenic process is represented by mutations in arterial smooth muscle cells, akin to formation of a benign tumor. These two theories can be harmonized, also taking into account the highly diversified nature of atherosclerotic lesions. Molecular epidemiology studies performed in our laboratory and other laboratories have shown that DNA adducts are systematically present in arterial smooth muscle cells, and their levels are correlated with atherogenic risk factors known from traditional epidemiology. Oxidative DNA damage was also consistently detected in these cells. The role of glutathione S-transferase polymorphisms on the frequency of the above molecular alterations and of arterial diseases is rather controversial. Prevention of both cancer and atherosclerosis is based on avoidance of exposure to risk factors and on fortification of the host defense mechanisms by means of dietary principles and chemopreventive drugs.