Role of CCR2 in the Development of Streptozotocin-Treated Diabetic Cardiomyopathy
Role of CCR2 in the Development of Streptozotocin-Treated Diabetic Cardiomyopathy
复制标题
CCR2 在链脲佐菌素治疗的糖尿病心肌病发生中的作用
DOI：
10.2337/db18-1231
复制
发表时间：
2019-11-01
期刊：
影响因子：
7.7
通讯作者：
Zhang, Fengxiao
中科院分区：
文献类型：
--
作者：
Tan, Xin;Hu, Lizhi;Zhang, Fengxiao
CCR2已被证明在糖尿病中起重要作用。然而，CCR2在糖尿病心肌病中的作用尚未被研究。在这项研究中，我们研究了心脏CCR2在糖尿病心肌病中的作用。我们建立了链脲佐菌素(STZ)诱导的糖尿病心肌病模型。CCR2在STZ诱导的糖尿病小鼠心脏中表达上调。CCR2基因敲除显著改善了STZ诱导的心功能障碍和纤维化。此外，CCR2的缺失抑制了STZ诱导的细胞凋亡和STZ诱导的心脏中活性氧的产生。CCR2基因敲除导致STZ处理小鼠心脏M2极化。Ccr2抑制剂治疗可逆转db/db小鼠高血糖引起的心功能障碍。这些结果表明，CCR2诱导的心脏炎症和氧化应激参与了糖尿病心肌病的发生，CCR2可能是一个新的治疗靶点。
CCR2 has been proven to play an important role in diabetes. However, the role of CCR2 in diabetic cardiomyopathy has not been examined. In this study, we investigated the effects of cardiac CCR2 on diabetic cardiomyopathy. We created a model of streptozotocin (STZ)–induced diabetic cardiomyopathy. Expression of CCR2 was upregulated in the hearts of STZ-induced diabetic mice. CCR2 knockout significantly improved STZ-induced cardiac dysfunction and fibrosis. Moreover, deletion of CCR2 inhibited STZ-induced apoptosis and the production of STZ-induced reactive oxygen species in the heart. CCR2 knockout resulted in M2 polarization in hearts of STZ-treated mice. Treatment with a CCR2 inhibitor reversed hyperglycemia-induced cardiac dysfunction in db/db mice. These results suggest that CCR2-induced inflammation and oxidative stress in the heart are involved in the development of diabetic cardiomyopathy and that CCR2 could be a novel target for therapy.