Induction and suppression of interferon‐inducible protein (IP)‐10 in reperfused myocardial infarcts may regulate angiogenesis

Abstract

SPECIFIC AIMSChemokines are chemotactic cytokines important in regulating angiogenesis. CXC chemokines containing the ELR motif, such as interleukin 8 (IL-8), are potent angiogenic factors, whereas CXC chemokines that lack the ELR motif, such as interferon-inducible protein 10 (IP-10), are potent angiostatic factors. Regulation of angiogenesis is dependent on the net biological balance between expression of angiogenic and angiostatic molecules in the injured tissue. In this study, we hypothesized that changes in the level of expression of the angiostatic CXC chemokine IP-10 have an important role in regulating neovessel formation after myocardial infarction.PRINCIPAL FINDINGS1. IP-10 mRNA induction after experimental canine myocardial infarctionWe used a canine model of circumflex coronary artery occlusion for 1 h, followed by reperfusion intervals ranging from 1 h to 28 days. We demonstrated a marked induction of IP-10 mRNA in the reperfused infarct after 1 h of coronary occlusion and 1 h of reperfusion. IP-10 mRNA expression remained high for 3 h (P<0.01, n=4) after reperfusion of the canine myocardium and was not detected at levels above controls after 10 h or 24 h of reperfusion (Fig. 1? ). No significant IP-10 mRNA up-regulation was noted after reperfusion intervals ranging from 24 h to 28 days. Figure 1.A) IP-10 up-regulation in the ischemic canine myocardium. Northern hybridization experiment demonstrating the time course of IP-10 mRNA expression after experimental canine myocardial infarction. IP-10 mRNA shows a marked transient induction in the ischemic canine myocardium, peaking after 1?3 h of reperfusion. IP-10 levels remain elevated for 5 h after reperfusion and return to control levels after 10 h. Spl, mRNA from the spleen of an endotoxin-stimulated animal. B) Quantitative analysis of IP-10 mRNA expression in experimental myocardial infarction. A significant increase in IP-10 mRNA levels was noted in ischemic segments when compared with the respective controls after 1 and 3 h of reperfusion (**P<0.01; n=4). In contrast, after 24 h of reperfusion IP-10 expression in ischemic myocardial segments returned to baseline levels (P