Role of Gi proteins in the regulation of blood pressure and vascular remodeling.

Yuan Li, Madhu B Anand-Srivastava

Biochemical pharmacology 2023 Feb

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Heterotrimeric guanine nucleotide regulatory proteins (G-proteins) through the activation of several signaling mechanisms including adenylyl cyclase/cAMP and phospholipase C (PLC)/phosphatidyl inositol (PI) turnover. regulate a variety of cellular functions, including vascular reactivity, proliferation and hypertrophy of VSMC. Activity of adenylyl cyclase is regulated by two G proteins, stimulatory (Gsα) and inhibitory (Giα). Gsα stimulates adenylyl cyclase activity and increases the levels of cAMP, whereas Giα inhibits the activity of adenylyl cyclase and results in the reduction of cAMP levels. Abnormalities in Giα protein expression and associated adenylyl cyclase\cAMP levels result in the impaired cellular functions and contribute to various pathological states including hypertension. The expression of Giα proteins is enhanced in various tissues including heart, kidney, aorta and vascular smooth muscle cells (VSMC) from genetic (spontaneously hypertensive rats (SHR)) and experimentally - induced hypertensive rats and contribute to the pathogenesis of hypertension. In addition, the enhanced expression of Giα proteins exhibited by VSMC from SHR is also implicated in the hyperproliferation and hypertrophy, the two key players contributing to vascular remodelling in hypertension. The enhanced levels of endogenous vasoactive peptides including angiotensin II (Ang II), endothelin-1 (ET-1) and growth factors contribute to the overexpression of Giα proteins in VSMC from SHR. In addition, enhanced oxidative stress, activation of c-Src, growth factor receptor transactivation and MAP kinase/PI3kinase signaling also contribute to the augmented expression of Giα proteins in VSMC from SHR. This review summarizes the role of Giα proteins, and the underlying molecular mechanisms implicated in the regulation of high blood pressure and vascular remodelling. Copyright © 2022 Elsevier Inc. All rights reserved.

Citation

Yuan Li, Madhu B Anand-Srivastava. Role of Gi proteins in the regulation of blood pressure and vascular remodeling. Biochemical pharmacology. 2023 Feb;208:115384