Ectopic Overexpression of PPAR gamma 2 in the Heart Determines Differences in Hypertrophic Cardiomyopathy After Treatment With Different Thiazolidinediones in a Mouse Model of Diabetes

作者全名："Cao, Xuemei; Mao, Min; Diao, Junlin; Hou, Yi; Su, Hong; Gan, Yongjun; Li, Jibin; Tong, Xiaoyong; Wu, Chaodong; Zuo, Zhong; Xiao, Xiaoqiu"

作者地址："[Cao, Xuemei; Diao, Junlin; Xiao, Xiaoqiu] Chongqing Med Univ, Affiliated Hosp 1, Dept Endocrinol, Chongqing, Peoples R China; [Cao, Xuemei; Mao, Min; Diao, Junlin; Hou, Yi; Su, Hong; Xiao, Xiaoqiu] Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Translat Med Major Metab Dis, Chongqing, Peoples R China; [Mao, Min; Su, Hong; Zuo, Zhong] Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiol, Chongqing, Peoples R China; [Hou, Yi; Gan, Yongjun] Chongqing Med Univ, Expt Teaching & Management Ctr, Chongqing, Peoples R China; [Li, Jibin] Chongqing Med Univ, Sch Publ Hlth & Management, Dept Nutr & Food Hyg, Chongqing, Peoples R China; [Tong, Xiaoyong] Chongqing Univ, Sch Pharmaceut Sci, Chongqing, Peoples R China; [Wu, Chaodong] Texas A&M Univ, Dept Nutr & Food Sci, College Stn, TX USA; [Cao, Xuemei] Chongqing Tongliang Dist Hosp Tradit Chinese Med, Chongqing, Peoples R China"

通信作者："Xiao, XQ (corresponding author), Chongqing Med Univ, Affiliated Hosp 1, Dept Endocrinol, Chongqing, Peoples R China.; Xiao, XQ (corresponding author), Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Translat Med Major Metab Dis, Chongqing, Peoples R China.; Zuo, Z (corresponding author), Chongqing Med Univ, Affiliated Hosp 1, Dept Cardiol, Chongqing, Peoples R China."

来源：FRONTIERS IN PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000674951800001

JCR分区：Q1

影响因子：5.6

年份：2021

卷号：12

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：cardiac hypertrophy; diabetic cardiomyopathy; insulin sensitizers; PPAR gamma; rosiglitazone

摘要："The clinical controversy of rosiglitazone as a hypoglycemic agent is potentially associated with heart failure, mainly due to its potent activation of peroxisome proliferator-activated receptor gamma (PPAR gamma). PPAR gamma partial agonists showed superior pharmacological profiles to rosiglitazone. This study compared differences in cardiac morphology and function of the PPAR gamma partial agonist CMHX008 with rosiglitazone. High-fat diet (HFD) induced obese mice, ob/ob mice and cardiomyocytes overexpressing PPAR gamma 2 were treated with CMHX008 or rosiglitazone. Heart function, myocardial morphology, and hypertrophy-related gene expression were examined. Clinical information from patients with type 2 diabetes mellitus (T2DM) who had taken rosiglitazone and undergone Doppler echocardiography was collected. HFD and ob/ob mice significantly developed cardiac contractile dysfunction, with upregulated PPAR gamma 2 protein levels in heart tissues. Cardiomyocytes of HFD and ob/ob mice were disorderly arranged, the cell areas expanded, and collagen accumulated. In vitro cardiomyocytes overexpressing PPAR gamma 2 displayed obvious structural abnormalities and high mRNA levels of ANP and BNP, critical cardiac hypertrophy-related genes. HFD-fed mice treated with rosiglitazone or CMHX008 had significantly improved cardiac function, but rosiglitazone induced higher expression of ANP and beta MHC and hypertrophic cardiomyopathy, while CMHX008 did not. Patients with T2DM taking rosiglitazone exhibited increased thickness of the posterior wall and the ventricular septum, suggesting cardiac hypertrophy. Our findings show that diabetic cardiomyopathy was associated with ectopic overexpression of PPAR gamma 2. The full agonist rosiglitazone prevents cardiac dysfunction at the expense of compensatory hypertrophy, while the partial agonist CMHX008 shared a comparable protective effect without altering the structure of cardiomyocytes."

基金机构："National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [82071734, 81871222, 81570763]; Fundamental Science and Advanced Technology Research of Chongqing [CSTC2019jcyjmsxm0425]"

基金资助正文："DThis research was funded by the National Natural Science Foundation of China (82071734, 81871222 and 81570763) and the Fundamental Science and Advanced Technology Research of Chongqing (CSTC2019jcyjmsxm0425)."