标题:Bladder drug mirabegron exacerbates atherosclerosis through activation of brown fat-mediated lipolysis
作者:Sui, Wenhai; Li, Hongshi; Yang, Yunlong; Jing, Xu; Xue, Fei; Cheng, Jing; Dong, Mei; Zhang, Meng; Pan, Huazheng; Chen, Yuguo; Zhan 更多
作者机构:[Sui, Wenhai; Li, Hongshi; Xue, Fei; Cheng, Jing; Dong, Mei; Zhang, Meng; Zhang, Cheng; Zhang, Yun] Shandong Univ, Key Lab Cardiovasc Remodeling & Fun 更多
通讯作者:Zhang, Y;Zhang, Y;Cao, YH
通讯作者地址:[Zhang, Y]Shandong Univ, Key Lab Cardiovasc Remodeling & Funct Res, Chinese Minist Educ, Chinese Natl Hlth Commiss,Qilu Hosp, Jinan 250012, Shandong, 更多
来源:PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
出版年:2019
卷:116
期:22
页码:10937-10942
DOI:10.1073/pnas.1901655116
关键词:mirabegron; atherosclerosis; plaque instability; lipolysis; adipose; tissue
摘要:Mirabegron (Myrbetriq) is a beta 3-adrenoreceptor agonist approved for treating overactive bladder syndrome in human patients. This drug can activate brown adipose tissue (BAT) in adult humans and rodents through the beta 3-adrenoreceptor-mediated sympathetic activation. However, the effect of the mirabegron, approved by the US Food and Drug Administration, on atherosclerosis-related cardiovascular disease is unknown. Here, we show that the clinical dose of mirabegron-induced BAT activation and browning of white adipose tissue (WAT) exacerbate atherosclerotic plaque de- velopment. In apolipoprotein E-/- (ApoE(-/-)) and low-density lipo- protein (LDL) receptor(-/-) (Ldlr(-/-)) mice, oral administration of clinically relevant doses of mirabegron markedly accelerates atherosclerotic plaque growth and instability by a mechanism of increasing plasma levels of both LDL-cholesterol and very LDL-cholesterol remnants. Stimulation of atherosclerotic plaque development by mirabegron is dependent on thermogenesis-triggered lipolysis. Genetic deletion of the critical thermogenesis-dependent protein, uncoupling protein 1, completely abrogates the mirabegron-induced atherosclerosis. Together, our findings suggest that mirabegron may trigger cardiovascular and cerebrovascular diseases in patients who suffer from atherosclerosis.
收录类别:SCIE
资源类型:期刊论文
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