Hypoxia extends the life span of vascular smooth muscle cells through telomerase activation

Chronic hypoxia induces smooth muscle cell proliferation and vessel wall re modeling in the vasculature of the lung. One well-characterized component o f the hypoxic response is transcriptional activation of genes encoding vasc ular smooth muscle cell (VSMC) mitogens. We report here that chronic hypoxi a call also prolong the growth of human VSMC by inducing telomerase activit y and telomere stabilization. We demonstrate that hypoxia induced phosphory lation of the telomerase catalytic component (TERT) and sustained high leve ls of TERT protein expression in VSMC compared to normoxia. Furthermore, in hibition of telomerase shortened cell life span in hypoxic cultures, wherea s constitutive expression of TERT extended the life span of cells tinder no rmoxic conditions. Our data indicate that hypoxic induction of telomerase a ctivity could be involved in long-term growth of VSMC and may thus contribu te to human vascular disorders.