| BackgroundStroke is the most fatal disease with an annual estimate of more than2million new cases and at least1.5million deaths in China from the the latest report at2008. In particular, about50%-70%of patients with stro-ke are ischemic. Atherosclerosis is the pivotal process in the development of ischemic stroke.Adipose tissue is not only a store for energy but also appears to be an active endocrine organ that produces many cytokines, which are kno-wn as adipokines. These adipokines appear to have systemic effects on the lymphoid organs, liver, muscles, gonads, brain, and vasculature. Adipokines have been implicated in the pathogenesis of atherosclerosis. It's known that adipose tissue can cause vascular complications either directly by causing atherosclerosis and inducing inflammatory responses, or indirectly by promoting the development of insulin resistance. These atherosclerosis-inducing pathways are mediated by kinds of adipokines, including adiponectin, leptin, tumor necrosis-alpha and resistin.Chemerin is recently discovered as an adipokine. It regulates the immune system and participates in inflammation by promoting the recur-itment of tissue macrophages and plasmacytoid dendritic cells as well, it is also associated with adipogenesis. As studies have shown that the lev- els of Chemerin are higher in the obesity and the patients with coronary disease. Therefore, we hypothesized that an increase in Chemerin might reflect carotid atherosclerosis and Chemerin levels might be related to the incidence of cerebral infarction. Endothelial cells dysfunction is the key point of the development of atherosclerosis. It has been reported that kinds of adipokines have important roles as vasoactive hormones which may impair endothelial function directly by altering vasoactive factor production and inciting endothelial cell activation. Whether Chemerin which was originally identified as a chemoattractant impact endothelial fuction directly? PART01Relationship between Chemerin Levels and Cerebral Infarction and AtherosclerosisObjectives1,To examined the levels of Chemerin in patients with cerebral infarction.2,To investigated the correlation with specific cardiometabolic parameters and also examed the relationship between the levels of Chemerin and cartiod atherosclerosis.MethodsIn the present study,148patients, all of whom had acute cerebral infarction within3days participated in this study and enrolled57healthy controls with no cerebrovascular disease. Their serum Chemerin levels and clinical parameters were measured. The serum chemerin levels of two groups of individals were determined by ELISA. All the patients under-gone ultrasound in order to calculate the carotid intima-media thickness (IMT) and detect the characters and quantity of cartiod atherosclerotic plaques. To divide into three group as the standard whether with the ex-istence of vulnerable plaque, stable plaque and normal. The serum che-merin levels were assessed by logistic regression in order to elucidate the relationship between Chemerin and cerebral infartion as well as vu-lnera-ble plaques. ResultsSerum Chemerin levels correlated positively with the carotid IMT and systolic blood pressure, Low density lipoprotein cholesterol, high sensitive C-reactive protein and Tumor necrosis factor-α levels. The case group has higher chemerin levels than the control and the levels are hig-her in the vulnerable plaques group. Multiple regression showed Che-merin was not an independent risk factor of cerebral infartion (OR:1.183;95%CI:0.743-1.885; P=0.479) nor an independent risk factor of vulnerable plaques (OR:1.018;95%CI:0.920-1.127; P=0.729)Conclusions:Serum Chemerin levels have a significant correlation with several pro-inflammation markers and metabolic risk factors as well as the caro-tid IMT in patients with acute cerebral infarction. However, multiple binary logistic regression showed Chemerin was not an independent risk factor of cerebral infarction nor vulnerable plaques. Additional investiga-tions are necessary to fully elucidate the role of Chemerin in cerebrovas-cular disease. PART02The Effects of Chemerin on Human Umbilical Vein Endothelial CellsObjectives1,To investigate the effect of Chemerin on Human Umbilical Vein Endothelial cells, we measure the level of nitric oxide(NO), inter-leukin-6(IL-6), intercellular adhesion molecule-1(ICAM-1) and vascular cell adhesion molecule-1(VCAM-1) after the stimulation of chemerin at different concentration at24hours and48hours respectively in vitro. And then to decide the optimal action time course and concentration.2. To explore the effects of Chemerin on TNF-alpha-treated HU-VECs-12which is the model of the research on impaired endothelial function. To investigate the effects of P13K/AKT-eNOS signal trans-duction pathway on vascular endothelial cells pretreated by chemerin.Methods1,HUVEC cells were cultured in serum-free medium before treatments for24h or48h with control groups and five different concen-trations groups(5,25,50,100,200ng/ml) of Chemerin. The total NO con-tent in cell medium by methods of Griess reagent and the protein levels of intercellular adhesion molecule-1(ICAM-1)/vascular cell molecule-1(VCAM-1) and Interleukin-6(IL-6) of HUVECs were detected by ELISA. 2,HUVECs stimulated by TNF-a(50ng/ml) in vitro.The total NO content in cell medium and the protein levels of ICAM-1/VCAM-1/IL-6of HUVECs were detected in the presence and absence of cheme-rin(100ng/ml), phosphatidylinositol3'-kinase(P13K) inhibitor LY-294002(20μmol/l) by the methods which had been mentioned above Intracellular signal molecules of P13k/AKT-eNOS signal such as Akt, phosphorylated-Akt,eNOS and phosphorylated-eNOS protein expres-sions were detected by western blot. The mRNA expression of Akt were measured by methods of realtime quantitative chain reaction polymerase.Results:1,Chemerin of (0-200ng/ml) significantly upregulated the levels of NO content.The increased expression of NO protein in chemerin-induced HUVECs was in a dose-dependent manner (P<0.05), These effects could partially diminished by cotreatment with LY294002.The protein levels of IL-6,intercellular adhesion molecule-1(ICAM-1) and vascular cell molecule(VCAM-1) of HUVECs hasn't been impacted.2,Chemerin(100ng/ml) significantly inhibited Tumor necrosis-alpha induced The expression of ICAM-1.VCAM-1and IL-6production (P<0.01). Chemerin also activated Akt and enhance the expression of phosphorylated-Akt,eNOS and phosphorylated eNOS protein (P<0.01) The expression of Akt protein and mRNA expression of Akt remain the same (P>0.05). These effects on the activate of P13k/Akt pathway signal could be partially diminished by cotreatment with LY294002,But the down-regulation of IL-6was not influenced.Conclusions:Chemerin may enhances the eNOS ability and attenuate the endothelin system and the overexpression of adhesion molecules in dysfunctional endothelial cells. Chemerin has the potential on improving endothelial function. P13K/Akt-eNOS signal transduction pathway may participate in the activity.A detailed molecular and functional analysisi of the role of chemerin in endothelial function should provide futher understanding of the relationship between Chemerin and endothelial function.
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