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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:23

Enthalten in:

International journal of molecular sciences - 23(2022), 19 vom: 03. Okt.

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

CXCR4
Cxcr4 protein, rat
Endothelial progenitor cells
Fibrosis
Inflammation
Ischemia
Journal Article
Left ventricular ejection fraction
Myocardial infarction
Percutaneous coronary intervention
Receptors, CXCR4
Reperfusion

Anmerkungen:

Date Completed 17.10.2022

Date Revised 19.10.2022

published: Electronic

Citation Status MEDLINE

doi:

10.3390/ijms231911730

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM347480969