Heterotrimeric g proteins in heart failure

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Structural remodeling of the heart, including myocardial hypertrophy and fibrosis, is a key determinant for the clinical outcome of heart failure. A variety of evidence indicates the importance of neurohumoral factors, such as endothelin-1, angiotensin II, and norepinephrine for the initial phase of the development of cardiac remodeling. These agonists stimulate seven transmembrane spanning receptors that are coupled to heterotrimeric GTP-binding proteins (G proteins) of the Gi, Gq and G12 subfamilies. The pathophysiological roles of each G protein-mediated signaling have been revealed by studies using transgenic and knockout mice. Using specific pharmacological tools to assess the involvement of G protein signaling pathways, we have found that diacylglycerolactivated transient receptor potential canonical (TRPC) channels (TRPC3 and TRPC6), one of the downstream effectors regulated by Gαq, work as a key mediator in the development of cardiac hypertrophy. In contrast, we also revealed that activation of Gα12 family proteins in cardiomyocytes mediates pressure overload-induced cardiac fibrosis. Stimulation of purinergic P2Y6 receptors by extracellular nucleotides released by mechanical stretch is a trigger of Gα12-mediated fibrotic responses of the heart. Although cardiac fibrosis is believed to accompany with Gαqmediated pathological hypertrophy that eventually results in heart failure, our results clearly show that cardiac fibrosis and hypertrophy are independent processes. These findings will provide a new insight into the molecular mechanisms underlying pathogenesis of heart failure.

Original languageEnglish
Title of host publicationHeart Failure
Subtitle of host publicationSymptoms, Causes and Treatment Options
PublisherNova Science Publishers, Inc.
Pages51-72
Number of pages22
ISBN (Electronic)9781617283147
ISBN (Print)9781616689599
Publication statusPublished - Jan 1 2010

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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    Nishida, M., Ohba, M., Nakaya, M., & Kurose, H. (2010). Heterotrimeric g proteins in heart failure. In Heart Failure: Symptoms, Causes and Treatment Options (pp. 51-72). Nova Science Publishers, Inc..