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

Abstract

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.