Evidence for DNA damage in patients with coronary artery disease

According to the "monoclonal hypothesis" of atherosclerosis, several studie s suggest that cancer and atherosclerosis may have several fundamental biol ogical mechanisms in common. Therefore, an increase in the mutation rate ma y be involved in the pathogenesis of atherosclerotic plaques. The aim of the study was to verify the presence of chromosomal damage in pe ripheral blood lymphocytes in patients with coronary artery disease by usin g micronucleus (MN) test, a reliable biomarker in genetic and cancer risk a ssessment. Subjects included 53 patients with documented coronary ischemic heart disea se (group I); 10 patients with valvular heart disease in absence of atheros clerotic lesions of the coronary arteries (group II) and 16 healthy subject s, age- and sex-matched (group III) were studied as controls. For each subj ect, two separate cultures were performed and 1000 binucleated cells were s cored for the evaluation of MN frequency. The mean (+/-S.E.M.) of MN frequency were 11.9 +/- 1.7, 5.9 +/- 1.2 and 3.6 +/- 0.7 in groups I, II and III, respectively. The MN frequency of group I was significantly higher than that of group m (P = 0.02). In group I, MN f requency increased with the number of affected Vessels (6.3 +/- 0.7, 13.9 /- 1.6, 14.9 +/- 5.3 for one-, two-, and three-vessel disease, respectively ). Scheffe's test showed that MN frequency was significantly higher in two- vessel compared with one-vessel disease (P = 0.0077). Moreover, a positive relationship was found between MN levels and the severity of the disease, c alculated by the Duke scoring system (R = 0.28, P = 0.032), as well as the systolic blood pressure (R = 0.34, P = 0.009). These results suggest that coronary artery disease in humans is a condition characterized by an increase of DNA damage, positively correlated with the severity of the atherosclerotic disease. (C) 2001 Elsevier Science B.V. AI I rights reserved.