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

• Published in: Nutrition, metabolism, and cardiovascular diseases Vol. 34; no. 6; pp. 1571 - 1580
• 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: Elsevier B.V 01.06.2024
• Subjects: Angiotensin II; Atherosclerosis; Autophagy; Hypertension; Mitochondrial KATP channel; Hypertension; Angiotensin II; Autophagy; Mitochondrial KATP channel; Atherosclerosis
• ISSN: 0939-4753; 1590-3729
• DOI: 10.1016/j.numecd.2024.01.019

The present study aimed to investigate whether the mitochondrial KATP 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 KATP channel-mediated autophagy contributes to Ang II-induced vascular dysfunction, development of hypertension, and atherosclerosis. •Angiotensin II accelerates the development of hypertension and atherosclerosis.•Angiotensin II induces abnormal lipid metabolism in the liver.•Oxidative stress is involved in the effects of angiotensin II.•The mitochondrial KATP channel mediates the effects of angiotensin II.•PI3K signal pathway contributes to the effects of angiotensin II.