Mitochondrial K ATP channel-mediated autophagy contributes to angiotensin II-induced vascular dysfunction in mice

• Published in: Nutrition, metabolism, and cardiovascular diseases Vol. 34; no. 6; p. 1571
• Main Authors: Yin, Xue-Min, Song, Yi-Yi, Jiang, Wen-Yi, Zhang, Hao-Tian, Chen, Jing-Wei, Murao, Koji, Han, Meng-Xiao, Sun, Wan-Ping, Zhang, Guo-Xing
• Format: Journal Article
• Language: English
• Published: Netherlands 01.06.2024
• Subjects: Angiotensin II; Animals; Aorta - drug effects; Aorta - metabolism; Aorta - pathology; Aorta - physiopathology; Atherosclerosis - chemically induced; Atherosclerosis - genetics; Atherosclerosis - metabolism; Atherosclerosis - pathology; Atherosclerosis - physiopathology; Autophagy - drug effects; Blood Pressure - drug effects; Diet, High-Fat; Disease Models, Animal; Hypertension - chemically induced; Hypertension - metabolism; Hypertension - pathology; Hypertension - physiopathology; Liver - drug effects; Liver - metabolism; Liver - pathology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout, ApoE; Nitric Oxide - metabolism; Potassium Channels; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; Vasodilation - drug effects; Hypertension; Mitochondrial K(ATP) channel; Atherosclerosis; Angiotensin II; Autophagy

The present study aimed to investigate whether the mitochondrial K channel contributes to angiotensin II (Ang II)-induced vascular dysfunction, the development of hypertension, and atherosclerosis. ApoE (-/-) mice fed a high-fat diet were chronically infused with Ang II for eight weeks and concomitantly treated with losartan (ARB), apocynin, or 5-hydroxy decanoate (5-HD), or 3-methyladenine (3-MA). Systolic blood pressure was measured, and pathological changes of aortic or liver tissue were observed. Nitric oxide (NO), superoxide dismutase 2 (SOD2) levels and vasorelaxation rate were measured, and protein and mRNA expressions were examined by western blot and RT-PCR. Ang II-induced development of hypertension was suppressed not only by ARB, and apocynin but also by 5-HD or 3-MA. Ang II infusion decreased aortic NO production and relaxation, as well as SOD2 activity in liver, which were improved by all treatments. In addition, Ang II-induced activation of autophagy was suppressed by 5-HD in aortic tissue, furthermore, Ang II increases the atherosclerotic index in plasma and exacerbates the development of atherosclerosis by increases of fat deposition in the aorta and liver. Lipid metabolism-related mRNA expressions (LXR-α, LDLR, SRBI, Acca, and FASN) were changed by Ang II. Similarly, not only ARB, and apocynin, but also 5-HD and 3-MA suppressed Ang II-induced these changes. Our present findings evidence that mitochondrial K channel-mediated autophagy contributes to Ang II-induced vascular dysfunction, development of hypertension, and atherosclerosis.