| Autor: |
Yeh KC; Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan 35053, Taiwan., Lee CJ; Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan 35053, Taiwan., Song JS; Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan 35053, Taiwan., Wu CH; Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan 35053, Taiwan., Yeh TK; Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan 35053, Taiwan., Wu SH; Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan 35053, Taiwan., Hsieh TC; Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan 35053, Taiwan., Chen YT; Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan 35053, Taiwan., Tseng HY; Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan 35053, Taiwan., Huang CL; Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan 35053, Taiwan., Chen CT; Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan 35053, Taiwan., Jan JJ; Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan 35053, Taiwan., Chou MC; Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan 35053, Taiwan., Shia KS; Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan 35053, Taiwan., Chiang KH; Taipei Heart Institute, Taipei Medical University, Taipei 11031, Taiwan.; Department of Cardiology, Taipei Medical University Hospital, Taipei 11031, Taiwan.; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.; Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 106319, Taiwan. |
| Abstrakt: |
CXCR4 antagonists have been claimed to reduce mortality after myocardial infarction in myocardial infarction (MI) animals, presumably due to suppressing inflammatory responses caused by myocardial ischemia-reperfusion injury, thus, subsequently facilitating tissue repair and cardiac function recovery. This study aims to determine whether a newly designed CXCR4 antagonist DBPR807 could exert better vascular-protective effects than other clinical counterparts (e.g., AMD3100) to alleviate cardiac damage further exacerbated by reperfusion. Consequently, we find that instead of traditional continuous treatment or multiple-dose treatment at different intervals of time, a single-dose treatment of DBPR807 before reperfusion in MI animals could attenuate inflammation via protecting oxidative stress damage and preserve vascular/capillary density and integrity via mobilizing endothelial progenitor cells, leading to a desirable fibrosis reduction and recovery of cardiac function, as evaluated with the LVEF (left ventricular ejection fraction) in infarcted hearts in rats and mini-pigs, respectively. Thus, it is highly suggested that CXCR4 antagonists should be given at a single high dose prior to reperfusion to provide the maximal cardiac functional improvement. Based on its favorable efficacy and safety profiles indicated in tested animals, DBPR807 has a great potential to serve as an adjunctive medicine for percutaneous coronary intervention (PCI) therapies in acute MI patients. |
