期刊
BIOMATERIALS
卷 97, 期 -, 页码 164-175出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2016.04.025
关键词
Relaxin gene therapy; Myocardial infarction; Bioreducible polymer; Dendrimer; Cardiac extracellular matrix (ECM); Post-infarct remodeling; Infarct-related coronary artery
资金
- National Research Foundation of Korea [2015R1A2A1A13027811, 2013M3A9D3045879]
- University of Utah [1S10RR027506-01A01]
- National Research Foundation of Korea [2013M3A9D3045879] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
In consensus, myocardial infarction (MI) is defined as irreversible cell death secondary to prolonged ischemia in heart. The aim of our study was to evaluate the therapeutic potential of anti-fibrotic human Relaxin-expressing plasmid DNA with hypoxia response element (HRE) 12 copies (HR1) delivered by a dendrimer type PAM-ABP polymer G0 (HR1/G0) after MI on functional, hemodynamic, geometric, and cardiac extracellular matrix (ECM) remodeling in rats. HR1/G0 demonstrated significantly improved LV systolic function, hemodynamic parameters, and geometry on 1 wk and 4 wks after MI in rats, compared with I/R group. The resolution of regional wall motional abnormalities and the increased blood flow of infarct-related coronary artery supported functional improvements of HR1/G0. Furthermore, HR1/G0 polyplex showed favorable post-infarct cardiac ECM remodeling reflected on the favorable cardiac ECM compositions. Overall, this is the first study, which presented an advanced platform for the gene therapy that reverses adverse cardiac remodeling after MI with a HR1 gene delivered by a bioreducible dendrimer polymer in the cardiac ECM. (C) 2016 Elsevier Ltd. All rights reserved.
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