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Published on: September 26, 2018
Oral administration of MnCl2 attenuated hyperlipidemia-related cardiac remodeling in ApoE-/- mice
Han-Xiao Zhang1, Cheng-Shun Zhang1, Rui-Zhen Huang2
1Acupuncture and Tuina School/Third Teaching Hospital, Chengdu University of Traditional Chinese Medicine, 37 Shi-er-qiao Road, Jinniu District, Chengdu, 610075, Sichuan, China.
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.
Insights
Manganese chloride (MnCl2) treatment reduced arrhythmias and improved heart function in hyperlipidemic mice. This suggests MnCl2 may delay cardiac remodeling and prevent arrhythmias in similar conditions.
Area of Science:
- Cardiovascular Science
- Pharmacology
- Biochemistry
Background:
- Yes-associated protein (YAP) inhibition by Manganese chloride (MnCl2) is known in hyperlipidemic mice.
- YAP is implicated in atherogenesis, but MnCl2's cardiac remodeling effects are understudied.
Purpose of the Study:
- To investigate the effects of MnCl2 on cardiac remodeling and supraventricular arrhythmia (SVA) in hyperlipidemic ApoE-/- mice.
Main Methods:
- Electrocardiography and echocardiography were used to assess cardiac function and arrhythmias.
- Oil Red O staining, lipid analysis, and histological staining (H&E, IHC, Masson's trichrome) evaluated plaque formation, inflammation, and fibrosis.
Main Results:
- MnCl2 treatment reduced the incidence of spontaneous SVA in ApoE-/- mice.
- Systolic function, reduced by hyperlipidemia, was restored by MnCl2.
- MnCl2 inhibited aortic plaque formation independently of lipid metabolism, reduced inflammatory cell infiltration, and decreased fibrosis.
Conclusions:
- MnCl2 effectively blocked spontaneous SVA and improved systolic function in a hyperlipidemia mouse model.
- MnCl2 demonstrates potential in delaying cardiac remodeling and reducing arrhythmia susceptibility in hyperlipidemia.
