Endothelial SIRT1 prevents age-induced impairment of vasodilator responses by enhancing the expression and activity of soluble guanylyl cyclase in smooth muscle cells

Cardiovascular Research
Yumeng GuoYu Wang

Abstract

Aged arteries are characterized by attenuated vasodilator and enhanced vasoconstrictor responses, which contribute to the development of diseases such as arterial hypertension, atherosclerosis and heart failure. SIRT1 is a longevity regulator exerting protective functions against vascular ageing, although the underlying mechanisms remain largely unknown. The present study was designed to elucidate the signaling pathways involved in endothelial SIRT1-mediated vasodilator responses in the arteries of young and old mice. In particular, the contributions of nitric oxide (NO), endothelial NO synthase (eNOS), cyclooxygenase (COX) and/or soluble guanylyl cyclase (sGC) were examined. Wild type (WT) or endothelial NO synthase knockout (eKO) mice were cross-bred with those overexpressing human SIRT1 selectively in the vascular endothelium (EC-SIRT1). Arteries were collected from the four groups of mice (WT, EC-SIRT1, eKO and eKO-SIRT1) to measure isometric relaxations/contractions in response to various pharmacological agents. Reduction of NO bioavailability, hyper-activation of COX signaling and down-regulation of sGC collectively contributed to the decreased vasodilator and increased vasoconstrictor responses in arteries of old WT mice...Continue Reading

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Citations

Sep 1, 2019·Current Pharmaceutical Design·Luca Liberale, Giovanni G Camici
Mar 27, 2019·The Journal of Pharmacology and Experimental Therapeutics·Vijayakumar SukumaranJames T Pearson
Mar 6, 2021·Molecular Therapy. Nucleic Acids·Xi YangYonghong Li
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Sep 28, 2021·Epigenetics : Official Journal of the DNA Methylation Society·Jitendra Kumar, Santosh Kumar
Nov 30, 2021·Journal of Cardiovascular Pharmacology·Musammat Kulsuma BegumYu Wang

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