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Updated: Jan 13, 2026

Shunt Surgery, Right Heart Catheterization, and Vascular Morphometry in a Rat Model for Flow-induced Pulmonary Arterial Hypertension
Published on: February 11, 2017
GLP-1 agonists reduce right ventricular mitochondrial dysfunction by inhibiting the GSK3β-Drp1 signalling in
Lin Zhao1, Yanghong Liu2, Ziwei Ou1
1Department of Cardiovascular Medicine, The Third Xiangya Hospital, Central South University, Changsha, 410013, China.
Abstract:
Right ventricular (RV) dysfunction is a critical complication of pulmonary hypertension (PH) with limited treatment strategies. This study evaluated the therapeutic efficacy of the GLP-1 agonist semaglutide on RV dysfunction in rodent PH models, focusing on mitochondrial dynamics and GSK3β-Drp1 signalling. Semaglutide significantly improved RV function, as evidenced by reduced right ventricular systolic pressure (RVSP), hypertrophy index (RV/LV + S), and improved echocardiographic parameters (RVEDA, RVFAC, TAPSE). Histological analysis revealed reduced RV hypertrophy and fibrosis, along with preserved mitochondrial ultrastructure in semaglutide-treated PH animals. Semaglutide restored GSK3β-Drp1 signalling, maintained mitochondrial membrane potential, and decreased mitochondrial fragmentation in primary cardiomyocytes via GLP-1R activation. Modulation of GSK3β expression further confirmed its role in GLP-1's protective effects. These findings collectively suggest that GLP-1 agonists, such as semaglutide, may represent a novel therapeutic strategy for RV dysfunction by targeting mitochondrial pathology and restoring critical signalling pathways like GSK3β-Drp1.
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