Short-term intermittent administration of CXCR4 antagonist AMD3100 facilitates myocardial repair in experimental myocardial infarction

• Published in: Acta biochimica et biophysica Sinica 2013-07, Vol.45 (7), p.561-569
• Main Authors: Luo, Yuechen, Zhao, Xiaoning, Zhou, Xin, Ji, Wenjie, Zhang, Ling, Luo, Tao, Liu, Hongmei, Huang, Tigang, Jiang, Tiemin, Li, Yuming
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; CXCR4; DNA Primers; Heterocyclic Compounds - administration & dosage; Heterocyclic Compounds - pharmacology; Heterocyclic Compounds - therapeutic use; Male; Myocardial Infarction - drug therapy; Myocardial Infarction - pathology; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Receptors, CXCR4 - antagonists & inhibitors; Reverse Transcriptase Polymerase Chain Reaction; 受体拮抗剂; 基质细胞衍生因子; 实验性; 心肌梗死; 短期; 给药; 间断
• ISSN: 1672-9145; 1745-7270
• DOI: 10.1093/abbs/gmt045

The binding of the stromal cell-derived factor-lα （SDF-lα） to the cysteine （C）-X-C motif chemokine receptor 4 （CXCR4） has emerged as a key signal for stem and pro-genitor cells trafficking to the circulation from the bone marrow. Our aim was to investigate the role of daily inter-mittent administration of AMD3100 （a specific reversible CXCR4 receptor antagonist） during the healing process after myocardial infarction （MI）. Wistar rats were sub- jected to MI and AMD3100 was injected intraperitoneally after surgery. SDF-lα mRNA expression was measured by real-time polymerase chain reaction. Histology changes were analyzed with immunofluorescence, Masson＇s tri-chrome staining, and wheat germ agglutinin. The number of leukocytes in peripheral blood was measured by com-plete blood cell count analysis. The activities of matrix metalloproteinase-2/9 （MMP-2/9） were determined by gelatin zymography. The expression level of SDF-lα mRNA in the infarcted tissue was enhanced rapidly （6 h）, peaked at 24 h, and then declined to the normal level at 7 days post-MI. AMD3100 further enhanced the increase of SDF-lα in infarct area. Increased leukocytes were observed in AMD3100-treated groups. The mobilization of c-kit＋ stem/progenitor cells and enhanced neovasculari-zation were augmented by AMD3100. Additionally, AMD3100 improved ventricular remodeling, which was revealed by the decrease of infarct size, viable cardiomyo-cyte cross-sectional area and left ventricle （LV） expansion index, and the increase of LV free wall thickness. The activities of MMP-2/9 were up-regulated by AMD3100. In conclusion, short-term intermittent administration of AMD3100 could accelerate the wound healing process in experimental MI and be a potential therapy for the treat- ment of MI.