Role of heparanase in pulmonary hypertension

Front Pharmacol. 2023 Aug 11:14:1202676. doi: 10.3389/fphar.2023.1202676. eCollection 2023.

Abstract

Pulmonary hypertension (PH) is a pathophysiological condition of increased pulmonary circulation vascular resistance due to various reasons, which mainly leads to right heart dysfunction and even death, especially in critically ill patients. Although drug interventions have shown some efficacy in improving the hemodynamics of PH patients, the mortality rate remains high. Hence, the identification of new targets and treatment strategies for PH is imperative. Heparanase (HPA) is an enzyme that specifically cleaves the heparan sulfate (HS) side chains in the extracellular matrix, playing critical roles in inflammation and tumorigenesis. Recent studies have indicated a close association between HPA and PH, suggesting HPA as a potential therapeutic target. This review examines the involvement of HPA in PH pathogenesis, including its effects on endothelial cells, inflammation, and coagulation. Furthermore, HPA may serve as a biomarker for diagnosing PH, and the development of HPA inhibitors holds promise as a targeted therapy for PH treatment.

Keywords: coagulation; glycocalyx; heparanase; inflammation; pulmonary hypertension; vascular endothelial cell.

Publication types

  • Review

Grants and funding

Science and Technology Project of Gansu Province, No. 22JR10KA 009; Science and Technology Department of Gansu Province, No. 20JR5RA35; Talent Innovation and Entrepreneurship Project of Science and Technology Bureau of Chengguan District, Lanzhou, No. 2020RCCX0030; Lanzhou Science and Technology Development Guiding Plan Project, No. 2019-ZD-37; Fund of The First Hospital of Lanzhou University, No. Ldyyyn2018-48.