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Molecular and Cellular Biology, May 2001, p. 3336-3342, Vol. 21, No. 10
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.10.3336-3342.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Hypoxia Extends the Life Span of Vascular Smooth Muscle Cells through Telomerase Activation

T. Minamino,dagger S. A. Mitsialis, and S. Kourembanas*

Department of Medicine, Division of Newborn Medicine, Children's Hospital, and Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115

Received 8 August 2000/Returned for modification 2 October 2000/Accepted 26 February 2001

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.

* Corresponding author. Mailing address: Division of Newborn Medicine, Children's Hospital, Enders 9, 300 Longwood Ave., Boston, MA 02115. Phone: (617) 355-7383. Fax: (617) 355-7677. E-mail: Stella.Kourembanas{at}tch.harvard.edu.

dagger Present address: Teikyo University Hospital, Chiba 0111, Japan.

Molecular and Cellular Biology, May 2001, p. 3336-3342, Vol. 21, No. 10
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.10.3336-3342.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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