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Hypoxia-mediated regulation of the secretory properties of mitral valve interstitial cells.

Authors
  • Salhiyyah, Kareem1
  • Sarathchandra, Padmini1
  • Latif, Najma1
  • Yacoub, Magdi H1
  • Chester, Adrian H2
  • 1 National Heart & Lung Institute, Imperial College London, Heart Science Centre, Harefield, Middlesex, United Kingdom. , (United Kingdom)
  • 2 National Heart & Lung Institute, Imperial College London, Heart Science Centre, Harefield, Middlesex, United Kingdom [email protected] , (United Kingdom)
Type
Published Article
Journal
AJP Heart and Circulatory Physiology
Publisher
American Physiological Society
Publication Date
Jul 01, 2017
Volume
313
Issue
1
Identifiers
DOI: 10.1152/ajpheart.00720.2016
PMID: 28314761
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The sophisticated function of the mitral valve depends to a large extent on its extracellular matrix (ECM) and specific cellular components. These are tightly regulated by a repertoire of mechanical stimuli and biological pathways. One potentially important stimulus is hypoxia. The purpose of this investigation is to determine the effect of hypoxia on the regulation of mitral valve interstitial cells (MVICs) with respect to the synthesis and secretion of extracellular matrix proteins. Hypoxia resulted in reduced production of total collagen and sulfated glycosaminoglycans (sGAG) in cultured porcine MVICs. Increased gene expression of matrix metalloproteinases-1 and -9 and their tissue inhibitors 1 and 2 was also observed after incubation under hypoxic conditions for up to 24 h. Hypoxia had no effect on MVIC viability, morphology, or phenotype. MVICs expressed hypoxia-inducible factor (HIF)-1α under hypoxia. Stimulating HIF-1α chemically caused a reduction in the amount of sGAG produced, similar to the effect observed under hypoxia. Human rheumatic valves had greater expression of HIF-1α compared with normal or myxomatous degenerated valves. In conclusion, hypoxia affects the production of certain ECM proteins and expression of matrix remodeling enzymes by MVICs. The effects of hypoxia appear to correlate with the induction of HIF-1α. This study highlights a potential role of hypoxia and HIF-1α in regulating the mitral valve, which could be important in health and disease.NEW & NOTEWORTHY This study demonstrates that hypoxia regulates extracellular matrix secretion and the remodeling potential of heart valve interstitial cells. Expression of hypoxia-induced factor-1α plays a role in these effects. These data highlight the potential role of hypoxia as a physiological mediator of the complex function of heart valve cells. Copyright © 2017 the American Physiological Society.

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