Hypoxia drives pulmonary artery smooth muscle cells (PASMCs) proliferation and phenotypic remodeling, processes central to vascular adaptation. Yaks, native to high-altitude environments, provide a natural model for studying cellular responses to chronic hypoxia. In this study, hypoxic exposure enhanced yak PASMCs proliferation and induced phenotypic transformation. Transcriptome profiling revealed that hypoxia suppresses microRNA-206 (miR-206), a regulator of vascular smooth muscle homeostasis. Loss of miR-206 activated the HIF-1α/BNIP3-dependent mitophagy pathway, increased mitophagy levels, and accelerated cell-cycle progression. Restoration of miR-206 reversed these effects, confirming its inhibitory role. Mechanistically, miR-206 directly targets the HIF-1α/BNIP3 signaling axis, linking noncoding RNA regulation to mitochondrial quality control under low oxygen. These findings define a miR-206-HIF-1α/BNIP3 regulatory circuit that coordinates mitophagy and phenotypic remodeling in yak PASMCs. This mechanism highlights the contribution of miRNA-mediated mitochondrial regulation to hypoxia adaptation and offers new insight into pulmonary vascular remodeling in high-altitude mammals.
Zhao et al. (Wed,) studied this question.