Oral administration of MnCl2 attenuated hyperlipidemia-related cardiac remodeling in ApoE-/- mice.
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| Abstract |
Manganese chloride (MnCl2) has been shown to inhibit the Yes-associated protein (YAP) in high-fat diet-fed ApoE-/- mice. Although YAP has been implicated in atherogenesis, there are limited data on the effects of MnCl2 on cardiac remodeling. In this study, we discovered, by electrocardiography, that hyperlipidemia led to spontaneous supraventricular arrhythmia (SVA) in ApoE-/- (KO) mice, with 3 of 9 KO + MnCl2 mice (33%) exhibiting lower incidence of spontaneous SVA than KO mice (6 of 10 mice, 60%). Echocardiography revealed that reduced systolic function in KO mice was reversed by MnCl2 treatment. Oil Red O staining of the aortas and biochemical analysis of lipid levels showed that MnCl2 inhibited plaque formation in a lipid metabolism-independent manner. MnCl2 inhibited inflammatory cell infiltration and reduced fibrosis, as evidenced by hematoxylin and eosin, immunohistochemical and Masson's trichrome staining, respectively. Our findings demonstrate that spontaneous SVA and reduced systolic function were blocked by MnCl2. Our findings show that MnCl2 was useful in delaying cardiac remodeling and reducing susceptibility to spontaneous SVA in a mouse model of hyperlipidemia.
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| Authors | Han-Xiao Zhang, Cheng-Shun Zhang, Rui-Zhen Huang, Xin Cao, Xiao-Qin Dai, Chuan-Yi Zuo, Peng Lv, Li-Juan Zhu, Shu-Guang Yu |
| Journal | Journal of pharmacological sciences (J Pharmacol Sci) Vol. 145 Issue 2 Pg. 167-174 (Feb 2021) ISSN: 1347-8648 [Electronic] Japan |
| PMID | 33451751 (Publication Type: Journal Article) |
| Copyright | Copyright © 2020 The Authors. Production and hosting by Elsevier B.V. All rights reserved. |
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