Elevated levels of oxidative DNA damage in patients with coronary artery disease.
BACKGROUND
Somatic DNA damage has been suggested to contribute to the pathogenesis of atherosclerosis. However, little is known about the role of oxidative DNA damage in patients with coronary artery disease (CAD).


METHODS
In this study, we used the comet assay to measure oxidative DNA damage (DNA strand breaks and enzyme-sensitive sites) in peripheral blood lymphocytes from 13 patients with angiographically documented CAD and 11 age- and sex-matched control participants.


RESULTS
Mean values of DNA strand breaks, oxidized pyrimidines and altered purines were significantly higher in CAD patients than in the control group (11.9 +/- 1.4, 18.0 +/- 2.7 and 18.1 +/- 3.1 compared with 3.3 +/- 0.2, 2.7 +/- 0.5 and 4.5 +/- 1.1; P < 0.0001, P < 0.0001 and P = 0.0009, respectively). Moreover, oxidized purines (for example, 8-oxo-guanine) increased with the number of affected vessels and positively correlated with the extent of CAD measured by means of the number of the coronary lesions (P = 0.76, P = 0.003) and the Duke scoring system (P = 0.66, P = 0.01). Diabetic patients showed higher levels of oxidized pyrimidines (31.3 +/- 5.5 compared with 14.1 +/- 2.7; P = 0.013), while patients with dyslipidemia had elevated altered purines compared with normal patients (20.4 +/- 2.6 compared with 4.9 +/- 3.1; P = 0.03).


CONCLUSIONS
These data indicate an overall elevation of oxidative DNA damage in CAD patients correlated with the severity of the disease and some atherogenic risk factors, suggesting a possible role of oxidative genetic damage in the pathogenesis of atherosclerosis.
Botto
Nicoletta
N
CNR, National Research COuncil, Institute of Clinical Physiology, Gaetano Pasquinucci Hospital, Massa, Italy. botto@ifc.cnr.it
Masetti
Serena
S
Petrozzi
Lucia
L
Vassalle
Cristina
C
Manfredi
Samantha
S
Biagini
Andrea
A
Andreassi
Maria G
MG
D020552:Comet Assay; D003327:Coronary Disease / Q000235:genetics*; D004249:DNA Damage / Q000502:physiology*; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004706:Endodeoxyribonucleases; D029968:Escherichia coli Proteins; D005260:Female; D006801:Humans; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011687:Purines / Q000032:analysis
D029968:Escherichia coli Proteins; D011687:Purines; D004706:Endodeoxyribonucleases; D043224:Deoxyribonuclease (Pyrimidine Dimer); C106403:NTH protein, E coli