CCR2 inhibitor strengthens the adiponectin effects against myocardial injury after infarction

Little evidence demonstrated the effects of nitric oxide (NO) hydrogel with adipocytes in vivo. We aimed to investigate the effects of Adiponectin (ADPN) and CCR2 Antagonist on cardiac functions and macrophage phenotypes after myocardial infarction (MI) using chitosan caged nitric oxide donor (CSNO) patch with adipocytes. 3T3-L1 cell line was induced to adipocytes and ADPN expression was knocked down. CSNO was synthesized and patch was constructed. MI model was constructed and patch was placed on the infarcted area. ADPN knockdown adipocytes or control was incubated with CSNO patch, and CCR2 Antagonist was also used to investigate the ADPN effects on myocardial injury after infarction. On day 7 after operation, cardiac functions of the mice using CSNO with adipocytes or ADPN knockdown adipocytes improved more than in mice only using CSNO for treatment. Lymphangiogenesis increased much more in the MI mice using CSNO with adipocytes. After treating with CCR2 Antagonist, Connexin43+ CD206+ cells and ZO-1+ CD206+ cells increased, suggesting that CCR2 Antagonist promoted M2 polarization after MI. Besides, CCR2 Antagonist promoted ADPN expression in adipocytes and cardiomyocytes. ELISA was also used and CKMB expression was much lower than other groups at 3 days after operation. On day 7 after operation, the VEGF and TGFβ expressions were high in the adipocytes CSNO group, illustrating that higher ADPN led to better treatment. In all, CCR2 Antagonist enhanced the ADPN effects on macrophage M2 polarization and cardiac functions. The combination used in border zone and infarcted areas may help improve patients' prognosis in surgery, such as CABG.

CCR2; CSNO hydrogel; adipocytes; adiponectin; lymphangiogenesis; macrophages.