| First Author | Sui W | Year | 2019 |
| Journal | Proc Natl Acad Sci U S A | Volume | 116 |
| Issue | 22 | Pages | 10937-10942 |
| PubMed ID | 31085638 | Mgi Jnum | J:276857 |
| Mgi Id | MGI:6307389 | Doi | 10.1073/pnas.1901655116 |
| Citation | Sui W, et al. (2019) Bladder drug mirabegron exacerbates atherosclerosis through activation of brown fat-mediated lipolysis. Proc Natl Acad Sci U S A 116(22):10937-10942 |
| abstractText | Mirabegron (Myrbetriq) is a beta3-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 beta3-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 development. In apolipoprotein E(-/-) (ApoE (-/-)) and low-density lipoprotein (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. |
