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Mitochondrial fission inhibition protects against hypertension induced by angiotensin II

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A Comment to this article was published on 10 April 2024

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.

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Acknowledgements

We thank Dr. Katherine J Elliott for critical comments.

Funding

This work was supported by the National Institutes of Health Grants (RO1 NS109382 and RO1 AG077780 to TH and SE, and R56 DK132859 to PO-O).

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Author notes

  1. These authors contributed equally: Kyle J. Preston, Tatsuo Kawai

Authors and Affiliations

  1. Department of Cardiovascular Science and Sol Sherry Thrombosis Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA

    Kyle J. Preston, Keiichi Torimoto, Ryohei Kuroda, Yuki Nakayama, Victor Rizzo & Satoru Eguchi

  2. Lemole Center for Integrated Lymphatics Research, Lewis Katz School of Medicine at Temple University, Philadelphia, PA, 19140, USA

    Tatsuo Kawai, Rosario Scalia & Michael V. Autieri

  3. Advanced Medical Research Center, Yokohama City University, Yokohama, 236-0004, Japan

    Tomoko Akiyama & Yayoi Kimura

  4. Barrow Aneurysm and AVM Research Center, Departments of Neurosurgery and Neurobiology Barrow Neurological Institute Phoenix AZ, Phoenix, AZ, USA

    Tomoki Hashimoto

  5. Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Patrick Osei-Owusu

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  1. Kyle J. Preston
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Correspondence to Satoru Eguchi.

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Preston, K.J., Kawai, T., Torimoto, K. et al. Mitochondrial fission inhibition protects against hypertension induced by angiotensin II. Hypertens Res 47, 1338–1349 (2024). https://doi.org/10.1038/s41440-024-01610-0

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