Mitochondrial fission inhibition protects against hypertension induced by angiotensin II.
Document Type
Article
Abstract
Mitochondrial dysfunction has been implicated in various types of cardiovascular disease including hypertension. Mitochondrial fission fusion balance is critical to mitochondrial quality control, whereas enhanced fission has been reported in several models of cardiovascular disease. However, limited information is available regarding the contribution of mitochondrial fission in hypertension. Here, we have tested the hypothesis that inhibition of mitochondrial fission attenuates the development of hypertension and associated vascular remodeling. In C57BL6 mice infused with angiotensin II for 2 weeks, co-treatment of mitochondrial fission inhibitor, mdivi1, significantly inhibited angiotensin II-induced development of hypertension assessed by radiotelemetry. Histological assessment of hearts and aortas showed that mdivi1 inhibited vessel fibrosis and hypertrophy induced by angiotensin II. This was associated with attenuation of angiotensin II-induced decline in mitochondrial aspect ratio seen in both the endothelial and medial layers of aortas. Mdivi1 also mitigated angiotensin II-induced cardiac hypertrophy assessed by heart weight-to-body weight ratio as well as by echocardiography. In ex vivo experiments, mdivi1 inhibited vasoconstriction and abolished the enhanced vascular reactivity by angiotensin II in small mesenteric arteries. Proteomic analysis on endothelial cell culture media with angiotensin II and/or mdivi1 treatment revealed that mdivi1 inhibited endothelial cell hypersecretory phenotype induced by angiotensin II. In addition, mdivi1 attenuated angiotensin II-induced protein induction of periostin, a myofibroblast marker in cultured vascular fibroblasts. In conclusion, these data suggest that mdivi1 prevented angiotensin II-induced hypertension and cardiovascular remodeling via multicellular mechanisms in the vasculature.
Keywords
Animals, Angiotensin II, Hypertension, Mitochondrial Dynamics, Mice, Inbred C57BL, Mice, Male, Quinazolinones, Vascular Remodeling, Blood Pressure
Medical Subject Headings
Animals; Angiotensin II; Hypertension; Mitochondrial Dynamics; Mice, Inbred C57BL; Mice; Male; Quinazolinones; Vascular Remodeling; Blood Pressure
Publication Date
5-1-2024
Publication Title
Hypertension research : official journal of the Japanese Society of Hypertension
ISSN
1348-4214
Volume
47
Issue
5
First Page
1338
Last Page
1349
PubMed ID
38383894
Digital Object Identifier (DOI)
10.1038/s41440-024-01610-0
Recommended Citation
Preston, Kyle J; Kawai, Tatsuo; Torimoto, Keiichi; Kuroda, Ryohei; Nakayama, Yuki; Akiyama, Tomoko; Kimura, Yayoi; Scalia, Rosario; Autieri, Michael V; Rizzo, Victor; Hashimoto, Tomoki; Osei-Owusu, Patrick; and Eguchi, Satoru, "Mitochondrial fission inhibition protects against hypertension induced by angiotensin II." (2024). Translational Neuroscience. 2389.
https://scholar.barrowneuro.org/neurobiology/2389