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

Pragya Sharma, Yu Dong, Virend Somers, Timothy E. Peterson, Yuebo Zhang, Shihan Wang, Guangxi Li, Prachi Singh

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 to a vasoconstrictive profile and to pathway-selective vascular IR, whereby insulin potentiates ET-1 expression. Moreover, IH may partly mediate its effects on NO and insulin-signaling via upregulating caveolin-1 expression.

Original languageEnglish (US)
Article number14110
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Caveolin 1
Endothelial Cells
Endothelin-1
Insulin
Nitric Oxide
Insulin Resistance
Nitric Oxide Synthase Type III
Vascular Resistance
Obstructive Sleep Apnea
Hypoxia
Blood Vessels
Coronary Vessels
Membrane Proteins
Phosphorylation

ASJC Scopus subject areas

  • General

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Intermittent hypoxia regulates vasoactive molecules and alters insulin-signaling in vascular endothelial cells. / Sharma, Pragya; Dong, Yu; Somers, Virend; Peterson, Timothy E.; Zhang, Yuebo; Wang, Shihan; Li, Guangxi; Singh, Prachi.

In: Scientific Reports, Vol. 8, No. 1, 14110, 01.12.2018.

Research output: Contribution to journalArticle

Sharma, Pragya ; Dong, Yu ; Somers, Virend ; Peterson, Timothy E. ; Zhang, Yuebo ; Wang, Shihan ; Li, Guangxi ; Singh, Prachi. / Intermittent hypoxia regulates vasoactive molecules and alters insulin-signaling in vascular endothelial cells. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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