Inhibition of CXCR4 ameliorates hypoxia-induced pulmonary arterial hypertension in rats

Am J Transl Res. 2021 Mar 15;13(3):1458-1470. eCollection 2021.ABSTRACTPulmonary vascular remodeling due to aberrant proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) is the main characteristic of pulmonary arterial hypertension (PAH). CXCR4 is a specific stem cell surface receptor of cytokine CXCL12 which could regulate homing of hematopoietic progenitor cells and their mobilization. There is evidence that bone marrow-derived CXCR4 proangiogenic cell accumulation take an important part in the development of pulmonary arterial hypertension; however, the underlying mechanisms still remain unknown. Here, we explored the expression profile of CXCR4 both in hypoxia rats and PAH patients by measuring proliferation and migration of PASMCs. We performed western blot analysis to detect downstream molecules. We demonstrated that CXCR4 expression level was increased in both rats exposed to chronic hypoxia and PAH patients in reconstructed pulmonary arterioles. The inhibition of CXCR4 expression slowed down the process of hypoxic-PAH by reducing the mean right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary vascular remodeling in vivo experimental mode. CXCR4 overexpression and inhibition regulated the cell growth of PASMCs in hypoxia condition, which are the critical cellular events in vascular disease. Furthermore, activation of β-catenin signaling and upregulation of CXCR4 could be blocked by AMD3100 both in vivo and vitro. Take...
Source: American Journal of Translational Research - Category: Research Authors: Source Type: research