Intermittent hypoxia regulates vasoactive molecules and alters insulin-signaling in vascular endothelial cells

Scientific Reports
Pragya SharmaPrachi Singh

Abstract

Vascular dysfunction and insulin resistance (IR) are associated with obstructive sleep apnea (OSA), which is characterized by frequent episodes of nocturnal intermittent hypoxia (IH). While it is recognized that the balance between vasoconstrictive (endothelin-1) and vasodilatory molecules (nitric oxide, NO) determine vascular profile, molecular mechanisms contributing to vascular dysfunction and IR in OSA are not completely understood. Caveolin-1 is a membrane protein which regulates endothelial nitric oxide synthase (eNOS) activity which is responsible for NO generation and cellular insulin-signaling. Hence, we examined the effects of IH on caveolin-1, eNOS, and endothelin-1 in human coronary artery endothelial cells in the context of IR. Chronic 3-day IH exposure up-regulated caveolin-1 and endothelin-1 expression while reducing NO. Also, IH altered insulin-mediated activation of AKT but not ERK resulting in increased endothelin-1 transcription. Similarly, caveolin-1 overexpression attenuated basal and insulin-stimulated NO synthesis along with impaired insulin-dependent activation of AKT and eNOS, with no effect on insulin-stimulated ERK1/2 phosphorylation and endothelin-1 transcription. Our data suggest that IH contributes...Continue Reading

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Citations

Feb 19, 2020·Pediatric Pulmonology·Masrur A KhanJoseph Mahgerefteh
Jun 3, 2020·The Journal of International Medical Research·Hong ChenMan Zhang
May 3, 2019·BMC Anesthesiology·Jun Xiong, Yongxing Sun
Dec 17, 2020·Frontiers in Physiology·Maider Varela-GuruceagaSoazig Le Lay
Jun 3, 2021·International Journal of Molecular Sciences·Jakub MocholAdrian Doroszko
Jun 3, 2021·International Journal of Molecular Sciences·David Sanz-RubioDavid Gozal
Sep 4, 2021·Mediators of Inflammation·Jichun HanYunyun Yue

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Methods Mentioned

BETA
ELISA
PCR
fluorescence imaging

Software Mentioned

ImageJ
JMP
SAS

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