Study on C-C motif chemokine receptor-2 positive exosomes inhibited monocytes infiltration in improving myocardial ischemia reperfusion injury
Li Yan
Liu Fengju
Li Xi
Yin Na
Abstract：Objective To investigate the mechanism of C-C motif chemokine receptor-2 positive(CCR2+)exosomes in regulating myocardial ischemia reperfusion(IR)injury in mice.Methods Twelve C57 mice were divided into wild-type(WT)sham-operated group,WT operated(IR model)group,CCR2-exosome operated group and CCR2+exosome operated group using a completely randomized method,with the last three groups constructing myocardial IR injury model and provide corresponding treatment.Ultrasound was used to examine the cardiac structure and function.Masson trichrome special staining method was used to detect the collagen deposition in cardiac tissues.Cardiomyocyte apoptosis was detected by transferase-mediated deoxyuridine triphosphate nick-end labeling method.The expressions of C-C motif chemokine ligand-2(CCL2)and CCR2 on the surface of monocytes were detected by immunohistochemical staining and real-time fluorescent quantitative polymerase chain reaction method.Flow cytometry was used to detect lymphocyte antigen 6 complex C(Ly6C)and CD43 monocytes in the infarct site after myocardial IR.Results At 7 d after myocardial IR surgery,the area of cardiac fibrosis in CCR2+exosome operated group was smaller than that in IR model group[(16.8±8.1)％vs(45.7±3.8)％];the ejection fraction was significantly lower than that of the WT sham-operated group but higher than that of the IR model group;the number of apoptotic cardiomyocytes in mice was less than that in IR model group.The relative expression of CCR2 protein in the heart of mice was lower than that of the IR model group;the area of CCR2 positive cells in the reperfusion area of the mice was smaller than that of the IR model group;the number of Ly6C+monocytes at the reperfusion site in mice was significantly lower than that in the IR model group;the number of monocytes in CD43 was significantly higher than that in IR model group;the relative expression of CCL2 mRNA and protein in the mouse heart was lower than that in the IR model group(all P＜0.05).Conclusions CCR2+exosomes show a significant anti-myocardial IR injury effect.The mechanism is that reduced CCL2 expression inhibits monocyte infiltration,thereby reducing myocardial injury and inhibiting heart failure.
Keywords：Ischemia-reperfusion injuryC-C motif chemokine receptor 2MonocyteInflammationMyocardial infarction
Publication Date：2024-05-08
Online Publishing Date：2026-09-14(First online date of this platform, not the publication date of the document)
Pages：5( 689-693 )