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Implication of G-proteins in Cardiovascular Disease

  • Chapter
Signal Transduction in the Cardiovascular System in Health and Disease

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 3))

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Abstract

Guanine nucleotide regulatory proteins (G-proteins) play a key role in the regulation of various signal transduction systems including adenylyl cyclase/cAMP and phospholipase C (PLC)/phosphatidylinositol turnover (PI) which are implicated in the modulation of a variety of physiological functions such as platelet functions, including platelet aggregation, secretion, and clot formation, and cardiovascular functions, including arterial tone and reactivity. Several abnormalities in adenylyl cyclase activity, cAMP levels, G-proteins, and PLC/PKC have been shown to be responsible for the altered cardiac performance and vascular functions observed in cardiovascular disease states. The enhanced or unaltered levels of inhibitory G-proteins (Giα-2 and Giα-3) and mRNA have been reported in different models of hypertension, whereas Gsα levels were shown to be unaltered. These changes in G-protein were associated with functions. The enhanced levels of Giα proteins precede the development of blood pressure and suggest that overexpression of Gi proteins may be one of the contributing factors for the pathogenesis of hypertension. The augmented levels of Giα proteins and associated adenylyl cyclase signaling in hypertension were shown to be attributed to the enhanced levels of vasoactive peptides. In addition, enhanced oxidative stress in hypertension may also be responsible for the enhanced expression of Giα proteins observed in hypertension. The levels of Gqα/11 and PLCβ have been shown to be upregulated in different models of hypertension. On the other hand, the levels of Gsα and not of Giα proteins were decreased in volume- or pressure-overload hypertrophy. The responsiveness of adenylyl cyclase to β-adrenergic agonists was also attenuated. In addition, the levels of Gqα were augmented in hypertrophy and the β-adrenergic receptor levels were decreased. Furthermore, the role of PKC in the development and progression of cardiac hypertrophy was also shown. Similarly, ischemia was shown to be associated with decreased, increased, or unaltered levels of Gsα, with decreased levels of Giα, and with decreased responsiveness of adenylyl cyclase to various stimuli such as β-adrenergic agonists, guanine nucleotides, forskolin, and others. Thus, the altered levels of G-proteins and associated signaling may be responsible for the impaired cardiovascular functions observed in hypertension, hypertrophy, and cardiac failure.

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  1. Department of Physiology, Research Centre, Centre hospitalier de l’Université de Montréal (CHUM) - Angus Campus, Faculty of Medicine, University of Montreal, Montreal, QC, Canada

    Madhu B. Anand-Srivastava

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  1. Department of Medicine, University of Montreal and Research Centre of the Centre Hospitalier de l’ Universite de Montreal, Montreal, PQ, H1W 4A4, Canada

    Ashok K. Srivastava

  2. Department of Physiology Faculty of Medicine, University of Montreal, Montreal, PQ, H3C3J7, Canada

    Madhu B. Anand-Srivastava

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Anand-Srivastava, M.B. (2008). Implication of G-proteins in Cardiovascular Disease. In: Srivastava, A.K., Anand-Srivastava, M.B. (eds) Signal Transduction in the Cardiovascular System in Health and Disease. Advances in Biochemistry in Health and Disease, vol 3. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-09552-3_1

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