Am J Cardiovasc Dis 2011;1(2):126-137
Original Article
GRK2 and beta-arrestins in cardiovascular disease: Something old,
something new
Anastasios Lymperopoulos
Department of Pharmaceutical Sciences, Nova Southeastern University College of Pharmacy, Ft. Lauderdale, FL 33328,
USA.
Received June 9, 2011; accepted June 25, 2011; Epub June 27, 2011; published July 30, 2011
Abstract: Heptahelical G protein-coupled receptors are the most diverse and therapeutically important family of receptors
in the human genome, playing major roles in the physiology of various organs/tissues including the heart and blood
vessels. Ligand binding activates heterotrimeric G proteins that transmit intracellular signals by regulating effector
enzymes or ion channels. G protein signaling is terminated, in large part, by phosphorylation of the agonist-bound receptor
by the family of G-protein coupled receptor kinases (GRKs) followed by arrestin binding, which uncouples the
phosphorylated receptor and G protein and subsequently targets the receptor for internalization. As the receptor-arrestin
complex enters the cell, arrestins serve as ligand-regulated scaffolds that recruit a host of intracellular proteins and
signal transducers, thus promoting their own wave of signal transduction independently of G-proteins. A large number of
preclinical studies in small and large animals over the past several years have pinpointed specific pathophysiologic roles
played by these two families of receptor-regulating proteins in various cardiovascular diseases, directly implicating them in
disease pathology and suggesting them as potential therapeutic targets. The present review gives an account of what is
currently known about the benefits of cardiac GRK2 inhibition for cardiovascular disease treatment, and also discusses the
exciting new therapeutic possibilities emerging from uncovering the physiological roles of adrenal GRK2 and of arrestin-
mediated signaling in vivo in the cardiovascular system. (AJCD1106002).
Keywords: Heptahelical receptor, cardiovascular disease, β-adrenergic receptor, GRK2, arrestin signaling, adrenal
gland, catecholamine, angiotensin II type 1 receptor, vascular smooth muscle.
Full Text PDF
Address all correspondence to:
Anastasios Lymperopoulos, PhD
Department of Pharmaceutical Sciences
Nova Southeastern University College of Pharmacy
3200 S. University Dr., HPD (Terry) Bldg/Room 1338
Ft. Lauderdale, FL, 33328, USA.
Tel.: 954-262-1338, FAX: 954-262-2278
E-mail: al806@nova.edu
Original Article
GRK2 and beta-arrestins in cardiovascular disease: Something old,
something new
Anastasios Lymperopoulos
Department of Pharmaceutical Sciences, Nova Southeastern University College of Pharmacy, Ft. Lauderdale, FL 33328,
USA.
Received June 9, 2011; accepted June 25, 2011; Epub June 27, 2011; published July 30, 2011
Abstract: Heptahelical G protein-coupled receptors are the most diverse and therapeutically important family of receptors
in the human genome, playing major roles in the physiology of various organs/tissues including the heart and blood
vessels. Ligand binding activates heterotrimeric G proteins that transmit intracellular signals by regulating effector
enzymes or ion channels. G protein signaling is terminated, in large part, by phosphorylation of the agonist-bound receptor
by the family of G-protein coupled receptor kinases (GRKs) followed by arrestin binding, which uncouples the
phosphorylated receptor and G protein and subsequently targets the receptor for internalization. As the receptor-arrestin
complex enters the cell, arrestins serve as ligand-regulated scaffolds that recruit a host of intracellular proteins and
signal transducers, thus promoting their own wave of signal transduction independently of G-proteins. A large number of
preclinical studies in small and large animals over the past several years have pinpointed specific pathophysiologic roles
played by these two families of receptor-regulating proteins in various cardiovascular diseases, directly implicating them in
disease pathology and suggesting them as potential therapeutic targets. The present review gives an account of what is
currently known about the benefits of cardiac GRK2 inhibition for cardiovascular disease treatment, and also discusses the
exciting new therapeutic possibilities emerging from uncovering the physiological roles of adrenal GRK2 and of arrestin-
mediated signaling in vivo in the cardiovascular system. (AJCD1106002).
Keywords: Heptahelical receptor, cardiovascular disease, β-adrenergic receptor, GRK2, arrestin signaling, adrenal
gland, catecholamine, angiotensin II type 1 receptor, vascular smooth muscle.
Full Text PDF
Address all correspondence to:
Anastasios Lymperopoulos, PhD
Department of Pharmaceutical Sciences
Nova Southeastern University College of Pharmacy
3200 S. University Dr., HPD (Terry) Bldg/Room 1338
Ft. Lauderdale, FL, 33328, USA.
Tel.: 954-262-1338, FAX: 954-262-2278
E-mail: al806@nova.edu
 |  |  |  |  |  |  |
| AJCD Copyright © 2011-present, All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711, USA |