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Strassheim et al. Vessel Plus 2018;2:29 Vessel Plus
DOI: 10.20517/2574-1209.2018.44

Review Open Access

A current view of G protein-coupled receptor -
mediated signaling in pulmonary hypertension:
finding opportunities for therapeutic intervention

Derek Strassheim , Vijaya Karoor , Kurt Stenmark , Alexander Verin , Evgenia Gerasimovskaya 2,3
1,2
1
4
2,3
1 Departments of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
2 Cardiovascular and Pulmonary Research laboratories, University of Colorado Denver, Aurora, CO 80045, USA.
3 Department of Pediatrics, Pulmonary and Critical Care Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
4 Vascular Biology Center, Augusta University, Augusta, GA 30912, USA.
Correspondence to: Dr. Derek Strassheim, Departments of Medicine, University of Colorado Denver, 12700 E. 19th Avenue, Box
B131, Research 2, Room 6470D, Aurora, CO 80045, USA. E-mail: derek.strassheim@ucdenver.edu

How to cite this article: Strassheim D, Karoor V, Stenmark K, Verin A, Gerasimovskaya E. A current view of G protein-coupled
receptor - mediated signaling in pulmonary hypertension: finding opportunities for therapeutic intervention. Vessel Plus
2018;2:29. http://dx.doi.org/10.20517/2574-1209.2018.44
Received: 8 Jun 2018 First Decision: 23 Jul 2018 Revised: 29 Aug 2018 Accepted: 30 Aug 2018 Published: 30 Sep 2018

Science Editor: Alexander D. Verin Copy Editor: Cai-Hong Wang Production Editor: Zhong-Yu Guo

Abstract
Pathological vascular remodeling is observed in various cardiovascular diseases including pulmonary hypertension
(PH), a disease of unknown etiology that has been characterized by pulmonary artery vasoconstriction, right ventricular
hypertrophy, vascular inflammation, and abnormal angiogenesis in pulmonary circulation. G protein-coupled receptors
(GPCRs) are the largest family in the genome and widely expressed in cardiovascular system. They regulate all
aspects of PH pathophysiology and represent therapeutic targets. We overview GPCRs function in vasoconstriction,
vasodilation, vascular inflammation-driven remodeling and describe signaling cross talk between GPCR, inflammatory
cytokines, and growth factors. Overall, the goal of this review is to emphasize the importance of GPCRs as critical signal
transducers and targets for drug development in PH.

Keywords: Pulmonary hypertension, vascular remodeling, vasoconstriction, vascular inflammation, GPCR, intracellular
signaling

INTRODUCTION
Pulmonary hypertension (PH) is a complex disease of unknown etiology. The pulmonary circulation re-
sponds to hypoxia by vasoconstriction, thereby diverting blood to oxygen rich regions. However, prolonged
hypoxic vasoconstriction leads to remodeling of pulmonary arteries (PAs) and increased PA pressure.

© The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0
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