Chaetocin attenuates atherosclerosis progression and inhibits vascular smooth muscle cell phenotype switching.

We aimed to explore the effect of chaetocin on atherosclerosis and its possible mechanism. In vitro, we observed that chaetocin treatment significantly inhibited the proliferation of VSMCs in concentration- and time-dependent manner. We also found that chaetocin suppressed the migration of VSMCs. Moreover, chaetocin treatment induced a contractile phenotype in VSMCs by increasing α-SMA and SM22α expression. In addition, chaetocin treatment attenuated the accumulation of H3K9me3 on VSMCs contractile gene promoters, which promoted the expression of α-SMA and SM22α. In vivo, chaetocin treatment decreased the H3K9me3 expression, diminished atherosclerotic plaque formation, and increased plaque stability by decreasing necrotic core area and lipid accumulation and increasing collagen content and contractile VSMC phenotype. We demonstrated a new function of chaetocin in inhibiting atherosclerosis progression and increasing plaque stability partly by inhibiting pathological phenotypic switching of VSMCs. These newly identified roles of chaetocin might provide a novel therapeutic target in atherosclerosis. © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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Ming-Yun Chen, Zhi-Hui Zhang, Jiang-Feng Ke, Ting-Ting Li, Mei-Fang Li, Jun-Xi Lu, Lian-Xi Li. Chaetocin attenuates atherosclerosis progression and inhibits vascular smooth muscle cell phenotype switching. Journal of cardiovascular translational research. 2022 Dec;15(6):1270-1282

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PMID: 35428928

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