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A cute ST-segment-elevation myocardial infarction (STEMI) is a leading cause of mortality and morbidity. Primary percutaneous coronary intervention (pPCI) is currently the most effective treatment strategy for STEMI. 1 However, acute restoration of myocardial blood flow may in itself jeopardize the cardiomyocytes. This phenomenon, known as reperfusion injury, may account for as much as 50% of the final myocardial infarct size, 2 a major determinant of the prognosis in patients with STEMI. 3 To date, few drugs have been shown to protect the heart during reperfusion. See Editorial by Flather See Clinical PerspectiveElevation of blood glucose is a common metabolic disorder among patients with acute myocardial infarction (AMI) and is associated with an adverse prognosis.5 Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates plasma glucose. GLP-1 may have antioxidant and anti-inflammatory properties and protect endothelial function. 6 Experimental studies have also revealed that GLP-1 or its analogs protect against reperfusion injury in pigs. 7 Liraglutide, a GLP-1 analog, was reported to reduce infarct size and improve cardiac output in normal and diabetic mice. 8 Several studies have shown that exenatide (another GLP-1 analog) protects against ischemia-reperfusion injury and reduces infarct size in patients with STEMI. 9,10 In our previous study, liraglutide could improve left ventricular (LV) function and reduce no-reflow in patients with AMI.11 No-reflow after AMI is an important predictor of infarct size and clinical outcome.12 However, the effects of liraglutide on infarct size in STEMI patients remain unclear. The aim of this study was to investigate the effects of liraglutide on myocardial salvage and infarct size using cardiac magnetic resonance (CMR) methods.Background-Liraglutide, a glucagon-like peptide-1 analog, was reported to reduce reperfusion injury in mice. We planned to evaluate the effects of liraglutide on reperfusion injury in patients with acute ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention. Methods and Results-A total of 96 patients with ST-segment-elevation myocardial infarction undergoing emergency primary percutaneous coronary intervention were randomized to receive either subcutaneous liraglutide or placebo. Study treatment was commenced 30 minutes before intervention (1.8 mg) and maintained for 7 days after the procedure (0.6 mg for 2 days, 1.2 mg for 2 days, followed by 1.8 mg for 3 days). The salvage index was calculated from myocardial area at risk, measured during the index admission (35±12 hours), and final infarct size measured at 91±5 days after primary percutaneous coronary intervention by cardiac magnetic resonance. At 3 months, the primary end point, a higher salvage index was found in the liraglutide group than in the placebo group in 77 patients evaluated with cardiac magnetic resonance (0.66±0.14 versus 0.55±0.15; P=0.001). The final infarct size was lower in the liraglutide group than that in the placebo ...

Vascular endothelial cells (ECs) appear to be one of the primary targets of hypoxia/reoxygenation (H/R) injury. In our previous study, we demonstrated that hepatocyte growth factor (HGF) exhibited a protective effect in cardiac microvascular endothelial cells (CMECs) subjected to H/R by inhibiting xanthine oxidase (XO) by reducing the cytosolic Ca2+ concentration increased in response to H/R. The precise mechanisms through which HGF inhibits XO activation remain to be determined. In the present study, we examined the signaling pathway through which HGF regulates Ca2+ concentrations and the activation of XO during H/R in primary cultured rat CMECs. CMECs were exposed to 4 h of hypoxia and 1 h of reoxygenation. The protein expression of XO and the activation of the phosphoinositide 3-kinase (PI3K), janus kinase 2 (JAK2) and p38 mitogen-activated protein kinase (p38 MAPK) signaling pathways were detected by western blot analysis. Cytosolic calcium (Ca2+) concentrations and reactive oxygen species (ROS) levels were measured by flow cytometry. The small interfering RNA (siRNA)-mediated knockdown of XO inhibited the increase in ROS production induced by H/R. LY294002 and AG490 inhibited the H/R-induced increase in the production and activation of XO. The PI3K and JAK2 signaling pathways were activated by H/R. The siRNA-mediated knockdown of PI3K and JAK2 also inhibited the increase in the production of XO protein. HGF inhibited JAK2 activation whereas it had no effect on PI3K activation. The siRNA-mediated knockdown of JAK2 prevented the increase in cytosolic Ca2+ induced by H/R. Taken together, these findings suggest that H/R induces the production and activation of XO through the JAK2 and PI3K signaling pathways. Furthermore, HGF prevents XO activation following H/R primarily by inhibiting the JAK2 signaling pathway and in turn, inhibiting the increase in cytosolic Ca2+.