M2b macrophages protect against myocardial remodeling after ischemia/reperfusion injury by regulating kinase activation of platelet-derived growth factor receptor of cardiac fibroblast

Yuan Yue; Suiqing Huang; Huayang Li; Wei Li; Jian Hou; Li Luo; Quan Liu; Cuiping Wang; Song Yang; Linhua Lv; Jinghua Shao; Zhongkai Wu

doi:10.21037/atm-20-2788

M2b macrophages protect against myocardial remodeling after ischemia/reperfusion injury by regulating kinase activation of platelet-derived growth factor receptor of cardiac fibroblast

Ann Transl Med. 2020 Nov;8(21):1409. doi: 10.21037/atm-20-2788.

Authors

Yuan Yue^{1

2}, Suiqing Huang¹, Huayang Li¹, Wei Li³, Jian Hou¹, Li Luo¹, Quan Liu¹, Cuiping Wang⁴, Song Yang⁴, Linhua Lv¹, Jinghua Shao⁵, Zhongkai Wu^{1

2}

Affiliations

¹ Department of Cardiac Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
² NHC Key Laboratory of Assisted Circulation, Sun Yat-sen University, Guangzhou, China.
³ Department of Medical Ultrasound, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
⁴ Department of Cardiothoracic Surgery ICU, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
⁵ Out-Patient Department, Shenxian Second People's Hospital, Shenxian, China.

Abstract

Background: Myocardial injury is a major cause of myocardial remodeling. Macrophages are important in cardiac repair as a result of their interactions with fibroblasts. As regulatory macrophages, M2b macrophages modulate inflammatory immune responses without participating in wound healing and could have enhanced protective effects on myocardial remodeling. Therefore, we tested the hypothesis that M2b macrophages could improve cardiac function and ameliorate myocardial fibrosis after the myocardial ischemia/reperfusion injury (MI/RI).

Methods: In vivo, MI/RI models were established with Sprague-Dawley (SD) rats and either M2b macrophages (MT group) or the same volume of vehicle (CK group) was injected into the ischemic zone. Two weeks after the operation, cardiac function and diameters were determined by echocardiography examination. Level of myocardial fibrosis was measured by Sirius red staining and the expression of fibrosis-related factors. In vitro, cardiac fibroblasts (CFs) were co-cultured with M2b macrophages or cultured with M2b macrophage supernatant. Expression of α-smooth muscle actin (α-SMA) and connective tissue growth factor (CCN2/CTGF) in the CFs were measured by western blotting and immunofluorescence staining. In addition, the expression of platelet-derived growth factors (PDGFs), the expression of platelet-derived growth factor receptors (PDGFRs) and the phosphorylation of PDGFRs was detected by western blotting.

Results: A significantly higher rat survival rate, improved left ventricular (LV) systolic function, decreased diameter of the LV and alleviated myocardial fibrosis were observed in the MT group than in the CK group. In vitro, the activation of CFs was significantly reduced by the M2b macrophages treatments, relative to the blank control. In addition, the kinase activation of PDGFRs was decreased by M2b macrophage treatments both in vivo and in vitro.

Conclusions: Our study demonstrated that the administration of M2b macrophages could attenuate myocardial remodeling after MI/RI. The regulation of the activation of PDGFRs in CFs is an important part of the protective mechanism.

Keywords: M2b macrophage; cardiac fibroblast (CF); myocardial ischemia/reperfusion injury (MI/RI); myocardial remodeling.