Protective effects of kaempferol against cardiac sinus node dysfunction via CaMKII deoxidization

Anatomy & Cell Biology
Minae An, Minsuk Kim

Abstract

Kaempferol exerts cardioprotective actions through incompletely understood mechanisms. This study investigated the molecular mechanisms underlying the cardioprotective effects of kaempferol in sinus node dysfunction (SND) heart. Here, we demonstrate that angiotensin II (Ang II) infusion causes SND through oxidized calmodulin kinase II (CaMKII). In contrast to this, kaempferol protects sinus node against Ang II-induced SND. Ang II evoked apoptosis with caspase-3 activation in sinus nodal cells. However, kaempferol lowered the CaMKII oxidization and the sinus nodal cell death. To block the CaMKII oxidization, gene of p47phox, a cytosolic subunit of NADPH oxidase, was deleted using Cas9 KO plasmid. In the absence of p47phox, sinus nodal cells were highly resistance to Ang II-induced apoptosis, suggesting that oxidized-CaMKII contributed to sinus nodal cell death. In Langendorff heart from Ang II infused mice, kaempferol preserved normal impulse formation at right atrium. These data suggested that kaempferol protects sinus node via inhibition of CaMKII oxidization and may be useful for preventing SND in high risk patients.

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Citations

Jan 22, 2018·Cardiovascular Toxicology·Anamika VishwakarmaDinesh Kumar
Nov 28, 2018·International Journal of Immunopathology and Pharmacology·Genglong ZhuZhidong Lin
Oct 23, 2019·Molecular Medicine Reports·Jing ZhaoJun Luo
Jul 28, 2020·The Annals of Thoracic Surgery·Qianqian ZhangRobina Matyal

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Methods Mentioned

BETA
fluorescence microscopy
transfection
protein assay
electrophoresis

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