Early upregulation of myocardial CXCR4 expression is critical for dimethyloxalylglycine-induced cardiac improvement in acute myocardial infarction.

Early upregulation of myocardial CXCR4 expression is critical for dimethyloxalylglycine-induced cardiac improvement in acute myocardial infarction.

Mayorga Mari; Kiedrowski Matthew; Shamhart Patricia; Forudi Farhad; Weber Kristal; Chilian William M; Penn Marc S; Dong Feng

American journal of physiology. Heart and circulatory physiology

2016

2016-01

The stromal cell-derived factor-1 (SDF-1):CXCR4 is important in myocardial repair. In this study we tested the hypothesis that early upregulation of cardiomyocyte CXCR4 (CM-CXCR4) at a time of high myocardial SDF-1 expression could be a strategy to engage the SDF-1:CXCR4 axis and improve cardiac repair. The effects of the hypoxia inducible factor (HIF) hydroxylase inhibitor dimethyloxalylglycine (DMOG) on CXCR4 expression was tested on H9c2 cells. In mice a myocardial infarction (MI) was produced in CM-CXCR4 null and wild-type controls. Mice were randomized to receive injection of DMOG (DMOG group) or saline (Saline group) into the border zone after MI. Protein and mRNA expression of CM-CXCR4 were quantified. Echocardiography was used to assess cardiac function. During hypoxia, DMOG treatment increased CXCR4 expression of H9c2 cells by 29 and 42% at 15 and 24 h, respectively. In vivo DMOG treatment increased

alpha Subunit/metabolism; Amino Acids; Animal; Animals; Apoptosis/drug effects; Cardiotonic Agents/*pharmacology; Cell Hypoxia; Cell Line; CXCR4/deficiency/genetics/*metabolism; Dicarboxylic/*pharmacology; Disease Models; Enzyme Inhibitors/pharmacology; hypoxia; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor-Proline Dioxygenases/antagonists & inhibitors/metabolism; Inbred C57BL; Knockout; Left/*drug effects; Mice; myocardial infarction; Myocardial Infarction/*drug therapy/genetics/metabolism/pathology/physiopathology; Myocardium/*metabolism/pathology; Rats; Receptors; Recovery of Function; Signal Transduction/drug effects; stem cells; Stem Cells/drug effects/metabolism; Stroke Volume/drug effects; Time Factors; Up-Regulation; Ventricular Function

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