Protective Effect of CXCR4 Antagonist DBPR807 against Ischemia-Reperfusion Injury in a Rat and Porcine Model of Myocardial Infarction: Potential Adjunctive Therapy for Percutaneous Coronary Intervention

Kai Chia Yeh, Chia Jui Lee, Jen Shin Song, Chien Huang Wu, Teng Kuang Yeh, Szu Huei Wu, Tsung Chin Hsieh, Yen Ting Chen, Huan Yi Tseng, Chen Lung Huang, Chiung Tong Chen, Jiing Jyh Jan, Ming Chen Chou, Kak Shan Shia, Kuang Hsing Chiang

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number11730
JournalInternational journal of molecular sciences
Volume23
Issue number19
DOIs
Publication statusPublished - Oct 2022

Keywords

  • CXCR4
  • endothelial progenitor cells
  • fibrosis
  • inflammation
  • ischemia
  • left ventricular ejection fraction
  • myocardial infarction
  • percutaneous coronary intervention
  • reperfusion

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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