Pathogenic Mechanisms of Pulmonary Arterial Hypertension: Homeostasis Imbalance of Endothelium-Derived Relaxing and Contracting Factors

Jinsheng Zhu; Lei Yang; Yangfan Jia; Angela Balistrieri; Dustin R Fraidenburg; Jian Wang; Haiyang Tang; Jason X-J Yuan

doi:10.1016/j.jacasi.2022.09.010

Pathogenic Mechanisms of Pulmonary Arterial Hypertension: Homeostasis Imbalance of Endothelium-Derived Relaxing and Contracting Factors

JACC Asia. 2022 Dec 15;2(7):787-802. doi: 10.1016/j.jacasi.2022.09.010. eCollection 2022 Dec.

Authors

Jinsheng Zhu¹, Lei Yang², Yangfan Jia², Angela Balistrieri³, Dustin R Fraidenburg⁴, Jian Wang^{1

3}, Haiyang Tang¹, Jason X-J Yuan³

Affiliations

¹ State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
² College of Veterinary Medicine, Northwest A&F University, Yangling, China.
³ Section of Physiology, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
⁴ Division of Pulmonary, Critical Care, Sleep, and Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.

Abstract

Pulmonary arterial hypertension (PAH) is a progressive and fatal disease. Sustained pulmonary vasoconstriction and concentric pulmonary vascular remodeling contribute to the elevated pulmonary vascular resistance and pulmonary artery pressure in PAH. Endothelial cells regulate vascular tension by producing endothelium-derived relaxing factors (EDRFs) and endothelium-derived contracting factors (EDCFs). Homeostasis of EDRF and EDCF production has been identified as a marker of the endothelium integrity. Impaired synthesis or release of EDRFs induces persistent vascular contraction and pulmonary artery remodeling, which subsequently leads to the development and progression of PAH. In this review, the authors summarize how EDRFs and EDCFs affect pulmonary vascular homeostasis, with special attention to the recently published novel mechanisms related to endothelial dysfunction in PAH and drugs associated with EDRFs and EDCFs.

Keywords: 5-HT, 5-hydroxytryptamine; ACE, angiotensin-converting enzyme; EC, endothelial cell; EDCF, endothelium-derived contracting factor; EDRF, endothelium-derived relaxing factor; ET, endothelin; PAH, pulmonary arterial hypertension; PASMC, pulmonary artery smooth muscle cell; PG, prostaglandin; TPH, tryptophan hydroxylase; TXA2, thromboxane A2; cGMP, cyclic guanosine monophosphate; endothelial dysfunction; endothelium-derived relaxing factor; pulmonary arterial hypertension; vascular homeostasis.

Publication types

Review