학술논문
Abstract 15231: The Synergy Between Angiopietin-1 and Cardiomyocyte Constitutes a Better Therapeutic Approach for Treatment of Myocardial Infarction
Document Type
Article
Author
Source
Circulation (Ovid); November 2019, Vol. 140 Issue: Supplement 1 pA15231-A15231, 1p
Subject
Language
ISSN
00097322; 15244539
Abstract
Introduction:Although cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSC) are being explored as a potential therapeutic approach for treatment of heart failure, hiPSC-CMs alone are unable to rebuild functional vessel network in ischemic myocardium.Hypothesis:The synergy between angiopoietin-1 (Ang-1) and CMs constitutes a better therapeutic approach for treatment of heart failure.Methods:Human CMs were differentiated from hiPSCs and purified by lactic acid. CMs were transfected with Ang-1 (Ang-1-CMs) or green fluorescence protein (GFP) (GFP-CMs) plasmids using liposomes. Gene transfection efficiency was characterized in vitro. Gene transfected CMs (1x106) were seeded into a fibrin/thrombin patch and implanted on the rat infarcted left ventricular anterior wall after myocardial infarction (MI). Echo function was determined at 1 and 6 weeks post-surgery. Immunohistochemistry study was performed at week-6 post MI.Results:The highest gene transfection efficiency was 54.5?8.9% based on GFP expression and cell viability was about 75%. Ang-1-CMs secreted Ang-1 protein up to 14 days, with peak level on day -2 post transefction (27.7?6.25 ng/ml) in vitro.Furthermore, Ang-1 protected CMs from lethal hypoxia through up-regulating pERK1/2 and inhibiting Bax protein expressions. In vivostudy showed that Ang-1-CMs transplantation more effectively limited cardiac cell or host CM apoptosis at 1-day post-MI as compared with GFP-CMs transplantation. Ang-1-CMs transplantation resulted in improved cell engraftment rate and arteriole formation and more effectively limited left ventricle (LV) dilation (EDV=460.7?96.1 ?l and ESV=219.8?72.9 ?l) and improved LV global pump function (EF=53.1?9%) as compared with MI (EDV=570.9?91.8 ?l, p=0.014; ESV=331.6?71.2 ?l, p=0.008; EF=42.3?4.1%, p=0.023) and GFP-CM transplantation (EDV=547.9?55.5 ?l, p=0.045; ESV=300.2?88.4 ?l, p=0.051; EF=46?10.9%,p=0.144).Conclusions:The synergy between Ang-1 and CMs more effectively improved left ventricular function in rat heart model of MI than CM only implantation.