"14,15-EET involved in the development of diabetic cardiac hypertrophy mediated by PPARs"

作者全名："Zhang, Jie; Yang, Chuang; Qiu, Hongmei; Yang, Junxia; Wu, Ke; Ding, Shumei; Jiang, Chengyan; Jiang, Qingsong"

作者地址："[Zhang, Jie; Yang, Chuang; Qiu, Hongmei; Yang, Junxia; Wu, Ke; Jiang, Qingsong] Chongqing Med Univ, Dept Pharmacol, Chongqing Key Lab Biochem & Mol Pharmacol, Chongqing 400016, Peoples R China; [Ding, Shumei] First Peoples Hosp Guangyuan, Dept Pharm, Guangyuan 628017, Sichuan, Peoples R China; [Jiang, Chengyan] First Peoples Hosp Zunyi, Dept Endocrinol, Zunyi 563000, Guizhou, Peoples R China"

通信作者："Jiang, QS (通讯作者)，Chongqing Med Univ, Chongqing 400016, Peoples R China."

来源：PROSTAGLANDINS & OTHER LIPID MEDIATORS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000751844900003

JCR分区：Q3

影响因子：2.9

年份：2022

卷号：159

期号：　

开始页：　

结束页：　

文献类型：Article

关键词："Diabetes; Cardiac hypertrophy; 14,15-EET; PPARs"

摘要："Cardiac hypertrophy is a key structural change in diabetic cardiomyopathy, which mechanism is unknown. 14,15-Epoxyeicosatrienoic acid (14,15-EET) generated from arachidonic acid by CYP2J2 has beneficial effects in metabolic syndrome, which also plays vital roles in inflammatory response. Peroxisome proliferator activated receptors (PPARs) are members of the nuclear receptor superfamily and have three subtypes of alpha, beta (or delta) and gamma. Studies have found that 14,15-EET can perform various biological functions by activating PPARs, but its role in diabetic cardiac hypertrophy is unknown. This study aimed to investigate the role of 14,15-EET-PPARs signaling pathway in the development of diabetic cardiac hypertrophy. Diabetic cardiac hypertrophy was developed by high-fat diet feeding combined with streptozotocin (40 mg/kg/d for 5 days, i.p.) in mice and was induced by glucose at 25.5 mmol/L (high glucose, HG) in H9c2 cells. The decreased level of 14,15-EET and the down regulated expression of PPAR alpha, PPAR beta and PPAR gamma were found following diabetic cardiac hypertrophy in mice. Similarly, both the level of 14,15-EET and the PPARs expression were also reduced in HG-induced hypertrophic cardiomyocytes. Supplementation with 14,15-EET improved the cardiomyocyte hypertrophy and up regulated PPARs expression, which were nullified by 14,15-EEZE, a 14,15-EET antagonist. Taken together, we conclude that the decreased 14,15-EET is involved in the development of diabetic cardiac hypertrophy through the down-regulation of PPARs."

基金机构："Natural Science Foundation of Chongqing, China [cstc2017jcjAX0211]; Guizhou Province Science and Technology Planned Project, China [[2017] 1210]"

基金资助正文："This work was supported by Natural Science Foundation of Chongqing, China (No. cstc2017jcjAX0211), and Guizhou Province Science and Technology Planned Project, China (No. [2017] 1210)."