1. Academic Validation
  2. CD248 as a novel therapeutic target in pulmonary arterial hypertension

CD248 as a novel therapeutic target in pulmonary arterial hypertension

  • Clin Transl Med. 2020 Sep;10(5):e175. doi: 10.1002/ctm2.175.
Tao Xu 1 Lei Shao 2 Aimei Wang 3 Rui Liang 3 Yuhan Lin 3 Guan Wang 1 Yan Zhao 1 Jing Hu 1 Shuangyue Liu 3
Affiliations

Affiliations

  • 1 Life Science Institute, Jinzhou Medical University, Jinzhou, P. R. China.
  • 2 Department of Cardiology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, P. R. China.
  • 3 Department of Physiology, Jinzhou Medical University, Jinzhou, P. R. China.
Abstract

Pulmonary vascular remodeling is the most important pathological characteristic of pulmonary arterial hypertension (PAH). No effective treatment for PAH is currently available because the mechanism underlying vascular remodeling is not completely clear. CD248, also known as endosialin, is a transmembrane protein that is highly expressed in pericytes and fibroblasts. Here, we evaluated the role of CD248 in pulmonary vascular remodeling and the processes of PAH pathogenesis. Activation of CD248 in pulmonary artery smooth muscle cells (PASMCs) was found to be proportional to the severity of PAH. CD248 contributed to platelet-derived growth factor-BB (PDGF-BB)-induced PASMC proliferation and migration along with the shift to more synthetic phenotypes. In contrast, treatment with Cd248 siRNA or the anti-CD248 therapeutic antibody (ontuxizumab) significantly inhibited the PDGF signaling pathway, obstructed NF-κB p65-mediated transcription of NOX4, and decreased Reactive Oxygen Species production induced by PDGF-BB in PAMSCs. In addition, knockdown of CD248 alleviated pulmonary vascular remodeling in rat PAH models. This study provides novel insights into the dysfunction of PASMCs leading to pulmonary vascular remodeling, and provides evidence for anti-remodeling treatment for PAH via the immediate targeting of CD248.

Keywords

CD248; NOX4; PDGF-BB; oxidative stress; pulmonary arterial hypertension.

Figures
Products