Activation of telomerase and expression of human telomerase reverse transcriptase in coronary atherosclerosis

Introduction: Considerable research on telomerase on human neoplastic and normal long-lived proliferative tissues has emerged. We explored the expression of telomerase in atherosclerotic human epicardial coronary arteries. Methods: Forty discrete human coronary arterial segments obtained from 19 heart transplant recipients were classified into nonatherosclerotic and atherosclerotic groups based on coronary angiography and histological examination. PCR-ELISA-based telomeric repeat amplification protocol (TRAP), and immunohistochemical analyses were conducted to determine the functional activity and cell-specific expression of telomerase. Results: Seventy percent of atherosclerotic coronary arteries exhibited positive telomerase activity, and the reactivation incidence reached fourfold higher than that of controls (P=.007). The telomerase catalytic protein, human telomerase reverse transcriptase (hTERT), was expressed in 88% of atherosclerotic tissues, a fivefold higher frequency compared with that of the controls. There was also a correlation of hTERT expression with the level of telomerase bioactivity (P=.017) and with the severity of atherosclerotic grade (P<.001). In comparison with the immunostaining of mitotic antigen, Ki-67, we found an association of hTERT expression with actively cycling cells in early lesions but with quiescent cells in late advanced atherosclerotic stages. Conclusions: The up-regulation of telomerase and its catalytic hTERT protein during stages of atherosclerotic evolution may implicate a role of telomerase in vascular remodeling underlying atherogenesis. ? 2005 Elsevier Inc. All rights reserved.