Protective mechanism of mitochondrial ALDH2 on hypoxic pulmonary hypertension by regulating autophagy

ObjectiveTo investigate the effect of activating mitochondrial aldehyde dehydrogenase on the autophagy of smooth muscle cells induced by hypoxia and the proliferation of pulmonary artery smooth muscle cells, and to analyze the regulation of mitochondrial aldehyde dehydrogenase on the proliferation of smooth muscle cells induced by hypoxia pulmonary arterial hypertension.

MethodsMale SD rats of SPF grade were divided into four groups: normal control group (N group), normoxia+ALDH2 agonist Alda-1 group (N+Alda-1 group), model group (H group), and hypoxia+Alda-1 group (H+Alda-1 group).PASMCs was divided into six groups: normoxia group (N group), normoxia+Alda-1 group (NA group), hypoxia group (H group), hypoxia+Alda-1 group (HA group), hypoxia+ALDH2 inhibitor Daidzin group (HD group), and hypoxia+Alda-1+Daidzin group (HAD group).HE staining was performed to observe the pathological changes of pulmonary artery in the lung tissue of each group, immunofluorescence was used to identify pulmonary artery smooth muscle cells, CCK-8 was applied to determine the cell viability and proliferation of each group, Annexin V-FITC/PI double staining was employed to detect apoptosis level, and Western blotting was used to analyze the protein expression of ALDH2, p62, Beclin1 and LC3B.

ResultsCompared with the N group, the walls of pulmonary arterioles was thickened and the lumen was narrowed in the H group.Compared with the H group, the thickness of pulmonary small artery wall was reduced, and the degree of stenosis was improved in the H+Alda-1 group.Compared with the group N, the expression of ALDH2 decreased (P < 0.05), the expression of autophagy-related proteins p62, Beclin1 and LC3B increased significantly (P < 0.01), and the cell proliferation increased significantly in the group H (P < 0.01).Compared with the group H, the expression of ALDH2 was significantly increased (P < 0.01), the expression of autophagy-related proteins p62, Beclin1 and LC3B obviously decreased (P < 0.01), and the cell proliferation was markedly inhibited in the HA group (P < 0.01).

ConclusionsMitochondrial ALDH2 has a significant inhibitory effect on the proliferation of hypoxia-induced PASMCs, and the mechanism may be related to the autophagy regulation of ALDH2 on cells.