The complicated lives of GPCRs in cardiac fibroblasts

Author:

Mazarura Grace R.1ORCID,Dallagnol Juliana C. C.123,Chatenet David2,Allen Bruce G.3ORCID,Hébert Terence E.1ORCID

Affiliation:

1. Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada

2. Institut National de la Recherche Scientifique, Centre Armand-Frappier Santé Biotechnologie, Groupe de Recherche en Ingénierie des Peptides et en Pharmacothérapie (GRIPP), Université du Québec, Laval, Quebec, Canada

3. Research Center, Montreal Heart Institute, Montreal, Quebec, Canada

Abstract

The role of different G protein-coupled receptors (GPCRs) in the cardiovascular system is well understood in cardiomyocytes and vascular smooth muscle cells (VSMCs). In the former, stimulation of Gs-coupled receptors leads to increases in contractility, whereas stimulation of Gq-coupled receptors modulates cellular survival and hypertrophic responses. In VSMCs, stimulation of GPCRs also modulates contractile and cell growth phenotypes. Here, we will focus on the relatively less well-studied effects of GPCRs in cardiac fibroblasts, focusing on key signaling events involved in the activation and differentiation of these cells. We also review the hierarchy of signaling events driving the fibrotic response and the communications between fibroblasts and other cells in the heart. We discuss how such events may be distinct depending on where the GPCRs and their associated signaling machinery are localized in these cells with an emphasis on nuclear membrane-localized receptors. Finally, we explore what such connections between the cell surface and nuclear GPCR signaling might mean for cardiac fibrosis.

Funder

Gouvernement du Canada | Canadian Institutes of Health Research

Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada

Publisher

American Physiological Society

Subject

Cell Biology,Physiology

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