Role of CCR2 in the Development of Streptozotocin-Treated Diabetic Cardiomyopathy.

Abstract

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 <i>db/db</i> 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.