Basic and Clinical Research Regarding Gene Expression of Predictive Biomarkers derived from Circulating Inflammatory Cells in Acute Myocardial Ischemia

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In the gene chip microarray analysis, we focused on Class A macrophage scavenger receptor (SR-A), which was the most strongly increased factor in the acute phase than in the chronic phase among the immune response factors according to the gene ontologic analysis. The SR-A mRNA levels of the peripheral circulating mononuclear cells were highest in the patients with acute coronary syndrome (p<0.01), while there was no significant difference between the control and the stable angina groups. The mRNA levels of SR-A in the coronary atheroscrelotic lesions obtained from directional coronary atherectomy were significantly higher in the patients with unstable angina than in the patients with stable angina (p<0.03). Furthermore, we examined the relationship between SR-A expression and prognosis in 73 patients with ischemic heart disease. Kaplan-Meier analysis demonstrated that patients with high SR-A mRNA levels had a significantly higher probability for the development of cardiovascular events … More .Next, we investigated the effects of CCR2 deficiency on myocardial ischemia-reperfusion injury in mice. Experiments were performed in CCR2^<-/-> and wild-type mice subjected to 45 minutes of ischemia followed by reperfusion. Macrophage infiltration in ischemic lesion was gradually increased and peaked at 3 days after reperfusion in wild-type nice. However, this process was markedly reduced in CCR2^<-1-> mice (P<0.01). Infarct size was significantly reduced in CCR2^<-/-> mice compared with wild-type mice at 3 days after reperfusion (P<0.001). In situ zymography revealed augmented gelatinolytic activity at 3 days after reperfusion in wild-type mice, but significantly less activity in CCR2^<-1-> mice. NADPH oxidase activity, the intensity of nitrotyrosine staining and expression of inducible nitric oxide synthase and thioredoxin-1 were significantly increased in ischemic myocardium in wild-type mice compared with CCR2^<-/-> mice, indicating a role for CCR2 in oxidative stress after ischemia-reperfusion. Less