医学
外体
微泡
射血分数
心肌梗塞
缺血性心肌病
心脏病学
HIF1A型
体内
心肌病
内科学
男科
血管生成
心力衰竭
生物
生物化学
基因
小RNA
生物技术
作者
Ming Wu,Arief Wibowo,Leen Delrue,Denise Veltman,Maarten Vanhaverbeke,Sander Trenson,Hilde Gillijns,Ellen Caluwé,Péter Pokreisz,Aernout Luttun,Jozef Bartúnek,Stefan Janssens
标识
DOI:10.1093/eurheartj/ehad655.1316
摘要
Abstract Introduction Blood outgrowth endothelial cell (BOEC)-derived exosomes can effectively induce vascular network formation in vitro and mediate therapeutic neovascularization in a skin wound healing model. We hypothesized that BOEC-derived exosomes can enhance myocardial repair in mice after ischemia-reperfusion (I/R) injury. Methods BOECs were isolated and culture-expanded from peripheral blood of patients with severe ischemic cardiomyopathy (ICMP) in normoxic and hypoxic (1% O2) conditions. Exosomes were isolated from the medium by differential ultracentrifugation, and their size, number, and surface markers were determined by nano tracking analysis (NTA) and immunoblot analysis. Myocardial infarction (MI) was induced via transient LAD ligation for 60 min followed by reperfusion. BOEC-derived exosomes and were resuspended in small fractions (120x10^8 particles per 10 µl) 2.5 µl 4 aliquots were injected under direct vision into the epicardial wall of the peri-infarct region. One month later, left ventricular (LV) structure and function were analyzed using a 7T Bruckner MRI with commercial software Segment in mice that received exosome injections or placebo injections (n=10 and n=8, respectively). Results Quantification of exosomes by NTA showed higher concentrations in the medium of BOECs cultured in hypoxia. Immunoblot analysis confirmed robust expression of exosome markers TSG101 and Flotilin-1. One month after intramyocardial exosome injections, heart rate, LV volumes or LV ejection fraction were similar between mice receiving myocardial exosomes injections (n=10) in the border zone as compared to those receiving placebo (n=8). However, in vivo exosome transfer mediated favorable structural remodeling after MI with lower LV mass indices (p=0.01) and better preserved regional wall thickness in all 4 segments receiving exosomes aliquots (p<0.05) (Figure). Conclusions Our results suggest that BOEC-derived exosomes have favorable post-infarction myocardial structural remodeling. Exosomes may constitute an attractive cell-free therapeutic modality.Figure
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