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

在基因芯片微阵列分析中，我们重点关注了A类巨噬细胞清道夫受体（SR-A），根据基因本体论分析，它是免疫反应因子中急性期比慢性期增加最强烈的因子。外周血循环单核细胞SR-A mRNA水平在急性冠脉综合征患者中最高（p<0.01），而对照组与稳定型心绞痛组之间差异无统计学意义。不稳定型心绞痛患者冠状动脉粥样硬化病变中SR-A mRNA水平明显高于稳定型心绞痛患者（p<0.03）。此外，我们检测了73例缺血性心脏病患者SR-A表达与预后的关系。Kaplan-Meier分析表明，高SR-A mRNA水平的患者发生心血管事件的可能性明显更高。接下来，我们研究了CCR2缺乏对小鼠心肌缺血再灌注损伤的影响。实验用CCR2^<-/->和野生型小鼠进行45min缺血再灌注。巨噬细胞在缺血病变处的浸润逐渐增加，在再灌注后3 d达到峰值。然而，CCR2^<-1->小鼠的这一过程明显减少（P<0.01）。再灌注3天后，CCR2^<-/->小鼠的梗死面积与野生型小鼠相比显著减小（P<0.001）。原位酶谱图显示野生型小鼠再灌注后3天明胶溶解活性增强，但CCR2^<-1->小鼠明胶溶解活性明显降低。与CCR2^<-/->小鼠相比，野生型小鼠缺血心肌NADPH氧化酶活性、硝基酪氨酸染色强度、诱导型一氧化氮合酶和硫氧还蛋白-1的表达均显著升高，提示CCR2在缺血再灌注后氧化应激中的作用。少

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