Therapeutic potential of cPLA2 inhibitor to counteract dilated-cardiomyopathy in cholesterol-treated H9C2 cardiomyocyte and MUNO rat

doi:10.1016/j.phrs.2020.105201

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/24636

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题名:	Therapeutic potential of cPLA2 inhibitor to counteract dilated-cardiomyopathy in cholesterol-treated H9C2 cardiomyocyte and MUNO rat
作者:	Huang, JP;Cheng, ML;Wang, CH;Huang, SS;Hsieh, PS;Chang, CC;Kuo, CY;Chen, KH;Hung, LM
关键词:	LysoPC;Non-obese metabolic syndrome;Dilated cardiomyopathy;cPLA2;Mitochondria
日期:	2020
上传时间:	2022-08-09T08:05:34Z (UTC)
出版者:	ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
ISSN:	1043-6618
摘要:	Background and purpose: The pathogenesis of cardiomyopathy in metabolically unhealthy obesity (MUO) has been well studied. However, the pathogenesis of cardiomyopathy typically associated with high cholesterol levels in metabolically unhealthy nonobesity (MUNO) remains unclear. We investigated whether cholesterol generated LysoPCs contribute to cardiomyopathy and the role of cytosolic phospholipase A2 (cPLA2) inhibitor in cholesterol-induced MUNO. Experimental approach: Cholesterol diet was performed in Sprague-Dawley rats that were fed either regular chow (C), or high cholesterol chow (HC), or HC diet with 10 % fructose in drinking water (HCF) for 12 weeks. LysoPCs levels were subsequently measured in rats and in MUNO human patients. The effects of cholesterol-mediated LysoPCs on cardiac injury, and the action of cPLA2 inhibitor, AACOCF3, were further assessed in H9C2 cardiomyocytes. Key results: HC and HCF rats fed cholesterol diets demonstrated a MUNO-phenotype and cholesterol-induced dilated cardiomyopathy (DCM). Upregulated levels of LysoPCs were found in rat myocardium and the plasma in MUNO human patients. Further testing in H9C2 cardiomyocytes revealed that cholesterol-induced atrophy and death of cardiomyocytes was due to mitochondrial dysfunction and conditions favoring DCM (i.e. reduced mRNA expression of ANF, BNP, DSP, and atrogin-1), and that AACOCF3 counteracted the cholesterol-induced DCM phenotype. Conclusion and implications: Cholesterol-induced MUNO-DCM phenotype was counteracted by cPLA2 inhibitor, which is potentially useful for the treatment of LysoPCs-associated DCM in MUNO.
URI:	http://dx.doi.org/10.1016/j.phrs.2020.105201 https://www.webofscience.com/wos/woscc/full-record/WOS:000598124500003 https://ir.csmu.edu.tw:8080/handle/310902500/24636
關聯:	PHARMACOLOGICAL RESEARCH ,2020 ,v160
显示于类别:	[中山醫學大學研究成果] 期刊論文

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