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

Molecular and Cellular Biology
Tohru MinaminoS Kourembanas

Abstract

Chronic hypoxia induces smooth muscle cell proliferation and vessel wall remodeling in the vasculature of the lung. One well-characterized component of the hypoxic response is transcriptional activation of genes encoding vascular smooth muscle cell (VSMC) mitogens. We report here that chronic hypoxia can also prolong the growth of human VSMC by inducing telomerase activity and telomere stabilization. We demonstrate that hypoxia induced phosphorylation of the telomerase catalytic component (TERT) and sustained high levels of TERT protein expression in VSMC compared to normoxia. Furthermore, inhibition of telomerase shortened cell life span in hypoxic cultures, whereas constitutive expression of TERT extended the life span of cells under normoxic conditions. Our data indicate that hypoxic induction of telomerase activity could be involved in long-term growth of VSMC and may thus contribute to human vascular disorders.

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Citations

Nov 19, 2010·Molecular Biology Reports·Aneta WojtylaBlazej Rubis
Feb 12, 2004·Journal of Molecular and Cellular Cardiology·Tohru MinaminoIssei Komuro
Apr 25, 2003·Experimental and Molecular Pathology·Ilene D AuerbachHarry V Vinters
Jan 5, 2002·Experimental Gerontology·E L OstlerR G A Faragher
Jan 16, 2002·Current Opinion in Genetics & Development·Dara L AisnerJerry W Shay
Sep 3, 2008·Nature Clinical Practice. Cardiovascular Medicine·Tohru Minamino, Issei Komuro
Feb 27, 2003·European Journal of Biochemistry·David LandoDaniel J Peet
Jul 31, 2007·Journal of Clinical Child and Adolescent Psychology : the Official Journal for the Society of Clinical Child and Adolescent Psychology, American Psychological Association, Division 53·Nancy E HillRoxanne Flint
May 15, 2002·Antioxidants & Redox Signaling·Stella Kourembanas
Jun 10, 2009·Antioxidants & Redox Signaling·Ehab H SarsourPrabhat C Goswami
Sep 28, 2002·Current Opinion in Lipidology·Tohru Minamino, Issei Komuro
Dec 23, 2006·Acta Pharmacologica Sinica·Feng-Xiang ZhangKe-Jiang Cao
Feb 19, 2009·Pigment Cell & Melanoma Research·Barbara Bedogni, Marianne Broome Powell
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