MMP8-mediated vascular remodeling in pulmonary hypertension

Pulmonary arterial hypertension (PAH) is a vascular remodeling disease that impacts the cardiopulmonary system. Due to the currently limited understanding of vascular remodeling, a cure for PAH remains elusive. This study highlights the critical role of the STAT1 (signal transducer and activator of transcription 1)/MMP8 (matrix metallopeptidase 8)/DRP1 (dynamin-related protein 1) axis in vascular remodeling and the pathogenesis of pulmonary hypertension. Notably, MMP8 is significantly elevated in pulmonary arterial endothelial cells and its levels correlate with the severity of the disease. MMP8 binds to and activates DRP1, inducing mitochondrial fragmentation and promoting a malignant phenotype of endothelial cells under hypoxic conditions. Moreover, MMP8 is tightly regulated by STAT1. The knockout of MMP8 attenuates chronic pulmonary vascular remodeling, and drugs targeting MMP8 alleviate pulmonary hypertension and enhance cardiac function. This study offers fresh insights into hypoxia-induced vascular remodeling, laying a theoretical foundation for countering vascular remodeling by directly regulating the STAT1/MMP8/DRP1 axis.