Interleukin-21 enhances angiogenesis and inhibits myocardial remodeling after myocardial infarction through targeting STAT3
Objective:To explore the effects of interleukin(IL)-21 on angiogenesis and cardiac remodeling in mice with myocardial infarction(MI)and its potential molecular mechanisms.Methods:Sixty rats were divided into sham operation group,MI group,and MI+IL-21 group,with 20 rats in each group.The MI model was established,and echocardiography was performed to measure the left ventricular end-systolic diameter(LVESD),left ventricular end-diastolic diameter(LVEDD),left ventricular ejection fraction(LVEF),and calculate the fractional shortening(FS)of the left ventricle.The myocardial infarction area and wall thickness were determined through 2,3,5-triphe-nyltetrazolium chloride(TTC)staining.The level of inflammation-related factors in serum was detected by ELISA.The TUNEL method was used to detect the apoptosis rate of myocardial tissue cells.Immunohistochemistry was used to assess the vascular density in the infarct border zone.Human umbilical vein endothelial cells(HUVECs)were divided into si-NC group,IL-21 group,si-signal transducer and activator of transcription 3(STAT3)group,and si-STAT+IL-21 group,and were cultured under hypoxic serum starvation(HSS)conditions for 24 hours to simulate ischemia.MTT,TUNEL,and angiogenesis assays were performed to evaluate cell viability,apoptosis,and angiogene-sis ability.qRT-PCR was used to detect the gene expression levels of IL-21,collagen type I alpha 1(COL1α1),matrix metalloproteinase-9(MMP-9),Caspase-3,and B-cell lymphoma-2(Bcl-2)in myocardial tissues.Western blot was used to detect the protein levels of IL-21,STAT3,p-STAT3,p38 mitogen-activated protein kinase(P38),p-P38,ser-ine/threonine protein kinase B(AKT),and p-AKT in myocardial tissues.Results:Compared with the sham surgery group,the MI group showed increases in infarct size,LVESD,LVEDD,serum IL-1β,COL1α1 in myocardial tissue,MMP-9 mRNA,apoptosis rate,Caspase-3 mRNA,expression levels of p-STAT3,p-AKT,and p-P38 proteins(all P＜0.05),and decreases in LVEF,FS,serum IL-21,IL-10,IL-21 mRNA and protein in myocardial tissue,and Bcl-2 mRNA(P＜0.05).Compared with the MI group,the MI+IL-21 group exhibited reductions in infarct size,LVESD,LVEDD,serum IL-1β,COL1α1 in myocardial tissue,MMP-9 mRNA,apoptosis rate,and Caspase-3 mRNA(all P＜0.05).Additionally,there were increases in LVEF,FS,serum IL-21,IL-10,IL-21 mRNA and protein in myocardial tissue,Bcl-2 mRNA,p-STAT3,p-AKT,p-P38 proteins,and vascular density(P＜0.05).Compared with the negative control group,the IL-21 group showed increased cell survival rate and tube formation length,along with a decrease in apoptosis rate(all P＜0.05).Conversely,the si-STAT3 group exhibited decreased cell survival rate and tube forma-tion length,accompanied by an increase in apoptosis rate(P＜0.05).Conclusion::IL-21 can stimulates angiogenesis,reduces inflammatory response and apoptosis,and improves cardiac remodeling after myocardial infarction,which may be related to the activation of the STAT3 pathway.
Myocardial infarctionInterleukin-21AngiogenesisSignal transducer and activator of transcrip-tion 3Cardiac remodelingInflammationApoptosis
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维普
