Evidence for DNA damage in patients with coronary artery disease.
According to the "monoclonal hypothesis" of atherosclerosis, several studies suggest that cancer and atherosclerosis may have several fundamental biological mechanisms in common. Therefore, an increase in the mutation rate may be involved in the pathogenesis of atherosclerotic plaques. The aim of the study was to verify the presence of chromosomal damage in peripheral blood lymphocytes in patients with coronary artery disease by using micronucleus (MN) test, a reliable biomarker in genetic and cancer risk assessment. Subjects included 53 patients with documented coronary ischemic heart disease (group I); 10 patients with valvular heart disease in absence of atherosclerotic lesions of the coronary arteries (group II) and 16 healthy subjects, age- and sex-matched (group III) were studied as controls. For each subject, two separate cultures were performed and 1000 binucleated cells were scored 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 III (P=0.02). In group I, MN frequency 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, calculated 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.
Botto
N
N
Laboratory of Cellular Biology, CNR Institute of Clinical Physiology, G. Pasquinucci Hospital, Via Aurelia Sud-Montepepe, 54100 Massa, Italy. botto@ifc.pi.cnr.it
Rizza
A
A
Colombo
M G
MG
Mazzone
A M
AM
Manfredi
S
S
Masetti
S
S
Clerico
A
A
Biagini
A
A
Andreassi
M G
MG
D000328:Adult; D016022:Case-Control Studies; D003327:Coronary Disease / Q000097:blood / Q000209:etiology / Q000235:genetics*; D004249:DNA Damage; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D015162:Micronucleus Tests; D008875:Middle Aged; D008954:Models, Biological; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors