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(Circulation Research. 2000;87:1085.)
© 2000 American Heart Association, Inc.

Editorial

G Proteins and Heart Failure

Is Gq a Novel Target for Heart Failure?

Giora Z. Feuerstein, Dennis Rozanski

From the Department of Cardiovascular Disease Research, DuPont Pharmaceuticals, Wilmington, Del.

Correspondence to G.Z. Feuerstein, Cardiovascular Disease Research, Experimental Station, Building 400-3255, Route 141 & Henry Clay Road, DuPont Pharmaceuticals, Wilmington, DE 19880. E-mail giora.z.feuerstein@dupontpharma.com

Key Words: heart failure • G protein • Gq • G protein–coupled receptors

	Introduction

 
Gproteins (GTP-binding proteins) are heterodimeric protein complexes consisting of , ß, and subunits. G proteins transduce signals from 7-transmembrane receptors (also known as G protein–coupled receptors [GPCRs]) to effector molecules. There are 20 distinct G subunits (40 000 molecular weight), 6 distinct ß subunits (35 000 molecular weight), and 12 subunits (8 000 molecular weight). The G is the major determinant of signaling selectivity, which is largely executed via one of the four major subfamilies: (1) G s: activation of adenylate cyclase; (2) G i/o: inhibition of adenylate cyclase; (3) Gq (Gq, G₁₁, G₁₄, G_15/16): activation of phospholipase C; and (4) G_12/13: function yet unclear.¹

Why is it important to research cardiac G proteins? The answer to this question is straightforward. First, GPCRs are present in the heart, and they transduce the major (if not the most important) signaling pathways associated with cardiac remodeling, as evidenced by the action of angiotensin II, endothelin-1, and the sympathetic neurohormonal systems on cardiac remodeling. Second, substantial alteration in the expression and function of G proteins occurs in heart failure, eg, increase in Gi.² Third, there are proven benefits of specific antagonists of GPCRs, eg, angiotensin II AT₁ receptors and ß-adrenergic receptor blockers, to induce beneficial reversal of cardiac remodeling in heart failure patients.³

In the past few years, attention has focused on the particular role of the Gq subtype of the G proteins in cardiac pathology, because Gq has been recognized . . . [Full Text of this Article]

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