Hypoxia promotes pulmonary vascular remodeling via HIF-1α to regulate mitochondrial dynamics.
Year: 2019
Type: article
Abstract: BACKGROUND: Increasing research suggests that mitochondrial defect plays a major role in pulmonary hypertension (PH) pathogenesis. Mitochondrial dynamics and quality control have a central role in the maintenance of the cell proliferation and apoptosis balance. However, the molecular mechanism underlying of this balance is still unknown. METHODS: To clarify the biological effects of hypoxic air exposure and hypoxia-inducible factor-1α (HIF-1α) on pulmonary arterial smooth muscle cell (PASMC) and pulmonary arterial hypertension rats, the cells were cultured in a hypoxic chamber under oxygen concentrations. Cell viability, reactive oxygen species level, cell death, mitochondrial morphology, mitochondrial membrane potential, mitochondrial function and mitochondrial biosynthesis, as well as fission-and fusion-related proteins, were measured under hypoxic conditions. In addition, rats were maintained under hypoxic conditions, and the right ventricular systolic pressure, right ventricular hypertrophy index and right ventricular weight/body weight ratio were examined and recorded. Further, we assessed the role of HIF-1α in the development and progression of PH using HIF-1α gene knockdown using small interfering RNA transfection. Mdivi-1 treatment was performed before hypoxia to inhibit dynamin-related protein 1 (Drp1). RESULTS: . Furthermore, HIF-1α also modulated mitochondrial dynamics in pulmonary vascular remodeling under hypoxia through directly regulating the expression of Drp1. CONCLUSIONS: In conclusion, our data suggests that abnormal mitochondrial dynamics could be a marker for the early diagnosis of PH and monitoring disease progression. Further research is needed to study the signaling pathways that govern mitochondrial fission/fusion in PH.
Source: PubMed
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2998196631