Regulation of YAP by Mammalian Target of Rapamycin Complex 1 in Endothelial Cells Controls Blood Pressure Through COX-2/mPGES-1/PGE2 Cascade

Hypertension
Liu YaoDing Ai

Abstract

Endothelial cells regulate vascular tone by producing both relaxing and contracting factors to control the local blood flow. Hypertension is a common side effect of mTORC1 (mammalian target of rapamycin complex 1) inhibitors. However, the role of endothelial mTORC1 in hypertension remains elusive. The present study aimed to determine the role of endothelial mTORC1 in Ang II (angiotensin II)-induced hypertension and the underlying mechanism. Endothelial mTORC1 activity was increased by Ang II both in vitro and in vivo. Blood pressure was higher in Tie-2-Cre-mediated regulatory associated protein of mTOR (mammalian target of rapamycin; Raptor) heterozygous-deficient (Tie2Cre-Raptor KD ) mice than control mice both before and after Ang II infusion. Acetylcholine-evoked endothelium-dependent relaxation of mesenteric arteries was impaired in Tie2Cre-Raptor KD mice. Treatment with indomethacin or a specific COX (cyclooxygenase)-2 inhibitor, NS-398, but not L-NG-nitroarginine methyl ester reduced endothelium-dependent relaxation in Raptorflox/- mice to a similar extent as in Tie2Cre-Raptor KD mice. Metabolomic profiling revealed that the plasma content of prostaglandin E2 was reduced in Tie2Cre-Raptor KD mice with or without Ang II...Continue Reading

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Citations

Oct 22, 2020·Cell Death & Disease·Dongying WangTianmin Xu
Mar 30, 2021·Clinical and Experimental Hypertension : CHE·Di LiuGuo-Xing Zhang
Jun 27, 2021·The FEBS Journal·Jiahong XieHongfeng Jiang
Jul 1, 2021·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·John J RehoKamal Rahmouni

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