Imperial College London
Alternate

Professor SirMagdiYacoub

Faculty of Medicine, National Heart & Lung Institute

Emeritus Professor
 
 
 
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Contact

 

+44 (0)1895 828 893m.yacoub

 
 
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Location

 

Heart Science Centre, HarefieldHarefield HospitalHarefield Hospital

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Summary

 

Publications

Citation

BibTex format

@article{Salhiyyah:2017:10.1152/ajpheart.00720.2016,
author = {Salhiyyah, K and Sarathchandra, P and Latif, N and Yacoub, MH and Chester, AH},
doi = {10.1152/ajpheart.00720.2016},
journal = {American Journal of Physiology: Heart and Circulatory Physiology},
pages = {H14--H23},
title = {Hypoxia-mediated regulation of the secretory properties of mitral valve interstitial cells},
url = {http://dx.doi.org/10.1152/ajpheart.00720.2016},
volume = {313},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Salhiyyah,K
AU  - Sarathchandra,P
AU  - Latif,N
AU  - Yacoub,MH
AU  - Chester,AH
DO  - 10.1152/ajpheart.00720.2016
EP  - 23
PY  - 2017///
SN  - 1522-1539
SP  - 14
TI  - Hypoxia-mediated regulation of the secretory properties of mitral valve interstitial cells
T2  - American Journal of Physiology: Heart and Circulatory Physiology
UR  - http://dx.doi.org/10.1152/ajpheart.00720.2016
UR  - http://www.ncbi.nlm.nih.gov/pubmed/28314761
UR  - http://hdl.handle.net/10044/1/59043
VL  - 313
ER  -
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