Cardiovascular Research Centre, Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.
FEBS Lett. 2021 Jun;595(12):1681-1695. doi: 10.1002/1873-3468.14091. Epub 2021 May 6.
Doxorubicin (DOX) is a very effective anticancer agent that is widely used in pediatric cancer patients. Nevertheless, DOX is known to have cardiotoxic effects that may progress to cardiomyopathy later in life. We have recently shown that cotreatment of resveratrol (RES) with DOX in juvenile mice attenuates late-onset hypertension-induced cardiomyopathy. However, the molecular mechanism responsible for these changes remains unknown. Herein, we show that the cardiac NLRP3 inflammasome plays a crucial role in regulating cardiac injury in a DOX -treated juvenile mouse model and the detrimental effects of hypertension in these mice later in life. We further demonstrate that RES significantly reduces systemic inflammation to contribute to the improvements observed in DOX -induced cardiac injury in young mice and late-onset hypertension-induced cardiomyopathy.
多柔比星（DOX）是一种非常有效的抗癌药物，广泛用于儿科癌症患者。然而，众所周知，DOX 具有心脏毒性作用，可能会在以后的生活中发展为心肌病。我们最近表明，在幼年小鼠中用白藜芦醇（RES）与 DOX 联合治疗可减轻晚期高血压诱导的心肌病。然而，导致这些变化的分子机制尚不清楚。在此，我们表明心脏 NLRP3 炎性小体在调节 DOX 处理的幼年小鼠模型中的心脏损伤以及这些小鼠以后生活中的高血压的有害影响中起着至关重要的作用。我们进一步证明 RES 可显著减轻全身炎症，有助于减轻 DOX 引起的幼年小鼠心脏损伤和晚期高血压诱导的心肌病。
