Oral administration of MnCl2 attenuated hyperlipidemia-related cardiac remodeling in ApoE−/− mice

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.