Hypoxia-induced PINK1/Parkin-mediated mitophagy promotes pulmonary vascular remodeling

Abstract

Pulmonary vascular remodeling (PVR) is not only the main pathophysiological feature of Pulmonary Artery Hypertension (PAH) but also the main reason for the progressive aggravation of PAH. Its central link is the excessive proliferation of pulmonary artery smooth muscle cells (PASMCs), which leads to the imbalance of proliferation/apoptosis, leads to the formation of PAH. At present, we found that hypoxia can up-regulate the expression of mitophagy protein PINK1/Parkin, induce the proliferation of PASMCs, and inhibit apoptosis. Knocking down PINK1^-/- and/or Parkin^-/-, found that the proliferation of PASMCs was significantly inhibited compared with that of PINK1/Parkin, while the proliferation of cells under PINK1^-/- Parkin^-/- was significantly lower than that of PINK1^-/- Parkin^+/+or PINK1^+/+ Parkin^-/-. These results suggest that hypoxia can activate the PINK1/Parkin-mediated mitophagy pathway, induce the excessive proliferation of PASMCs, eventually lead to PVR, leading to HPH. Our team is further exploring which substances in HPH can induce mitotic response, which molecules specifically mediate the activation of mitotic pathways, and what role they play in the occurrence and development of HPH disease.

Keywords: Hypoxia; Mitophagy; Pulmonary artery hypertension (PAH); Pulmonary artery smooth muscle cells (PASMCs); Pulmonary vascular remodeling (PVR).