Telomere Shortening in Human Coronary Artery Diseases

BACKGROUND: Increased cell turnover in response to injury is considered to be important in the development of atherosclerotic plaques. Telomere shortening has been shown to be associated with cell turnover. We assessed the telomere length of human coronary endothelial cells to clarify whether there is a relationship between telomere shortening and coronary artery disease (CAD). METHODS AND RESULTS: Coronary endothelial cells were obtained from 11 patients with CAD who underwent autopsy and 22 patients without CAD who underwent autopsy by scraping off the luminal surface of coronary arteries. DNA extracted from the endothelial cells were blotted and hybridized with telomere-specific oligonucleotide (TTAGGG4). The hybridization signal intensity, which represented telomeric DNA content, was standardized with centromeric DNA content (T/C ratio) to estimate telomere length. The T/C ratios were significantly smaller (P<0.0001) in CAD patients than in age-matched non-CAD patients (CAD patients, 0.462+/-0.135; non-CAD patients, 1.002+/-0.212). In 6 individual CAD patients, the T/C ratio at the atherosclerotic lesion was significantly smaller (P<0.05) than that at the non-atherosclerotic portion. CONCLUSIONS: These findings suggest that focal replicative senescence and telomere shortening of endothelial cells may play a critical role in coronary atherogenesis and CAD.