The sophisticated function of the mitral valve depends to a large extent on the extracellular matrix (ECM) and specific cellular components. These are tightly regulated by a repertoire of mechanical stimuli and biological pathways. One potentially important pathway is hypoxia. The purpose of this investigation is to determine the effect of hypoxia on the regulation of mitral valve interstitial cells (MVIC) with respect to the synthesis and secretion of extracellular matrix proteins. Hypoxia resulted in reduced production of total collagen and sulphated glycosaminoglycans (sGAG) in cultured porcine MVIC. Increased gene expression of matrix metalloproteinases 1 and 9 and their tissue inhibitors 1 and 2 was also observed following incubation under hypoxic conditions for up to 24 hours. Hypoxia had no effect on VIC viability, morphology or phenotype. MVIC expressed hypoxia-inducible factor 1-α (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 to normal or myxomatous degenerated valves. In conclusion, hypoxia affects the production of certain ECM proteins and expression of matrix remodelling enzymes by MVIC. The effects of hypoxia appear to be mediated by the induction of HIF-1α. This study highlights a potential role of hypoxia and HIF-1α in regulating the MV, which could be important in health and disease.
- Mitral Valve
- interstitial cells
- Extracellular matrix
- Hypoxia-inducible factor 1-α
- Copyright © 2016, American Journal of Physiology-Heart and Circulatory Physiology