1、The Novel Function Of IC53-Its Role And Underlying Mechanism In Promoting Atherosclerosis 2、 Low Estimated Glomerular Filtration Rate Is Associated With High Recurrence Rate And Poor Prognosis Of Stroke-A Prospective Study

Object:Atherosclerosis, a primary cause of coronary artery disease (CAD) and stroke, is a chronic inflammation disease caused by multiple factors including genetic factors and environmental factors. The mechanism underlying atherosclerosis involves abnormal lipids metabolism, inflammation, dysfunction of immunity system and endothelia, and genetic factros. In our previous study, we found a gene named IC53, which was expressed in the macrophage of atherosclerosic plaque and promoted angiogenesis. This result led us to hypothesize that IC53 may promote atherosclerosis through inflammation.Methods:To test our hypothesis, first, we performed western bolt to detect the protein levels of IC53 after HUVEC cells were treated with ox-LDL; and then, we investigated whether IC53 promote adhesion between monocyte and endothelial cells and migration of HUVEC. Furthermore, we used qRT-PCR method to test the expression of inflammatory cytokines (MCP-1, ICAM, VCAM) after THP-1 and HUVEC cells were transfected with siRNA which can knockdown IC53 or adenovirus which can overexpress IC53. We described the gene level change in THP-1 cells from 3 siRNA-transfected and 3 control using Affymetrix HTA2.0 Chip. Finally, we dissected its underlying mechanism of regulating inflammatory cytokines through Co-immunoprecipitation and Mass Spectrometry.Results:When HUVEC cells were treated with different concentrations of ox-LDL (25μg/ml,50μg/ml, 100μg/ml) for 48h, increased expression of IC53 were obversed. When HUVEC cells were treated with ox-LDL (100μg/ml) for 48h, compared with the control group, the expression of IC53 was increased to 2.4-fold. And then, we found that the reducing expression of IC53 prevent adehision of THP-1 and migration of HUVEC (0.31-fold,P=0.007 and 0.84-fold, P=0.04 respectively). After we used RNAi to knockdown the IC53, the decreased mRNA levels of MCP-1 (0.4-fold, P<0.001), ICAM (0.75-fold, P<0.001) and VCAM (0.75-fold, P<0.001) were detected significantly. Whereas the increased mRNA level of MCP-1 (2.8-fold, P<0.05) were observed significantly after upregulation of IC53. After analyzing the results of chips, we found that that the gene level of MCP-1、TLR8、EFTUD2 decreased in siRNA-transfected. Furthermore, Co-immunoprecipitation and Mass Spectrometry study indicated that IC53 may regulate MCP-1 through HSP27, annexin A2, MYO1E, sulforaphane.Conclusion:Our study showed that IC53 can promote atherosclerotic inflammation reaction and provide a novel target for prevention and therapy of atherosclerosic disease. Targeted intervention in inflammation disorders would delay the process of plaque formation and disruption.Object:This study investigated whether a low estimated glomerular filtration rate (eGFR) leads to a higher risk of stroke recurrence and a poor prognosis in hemorrhagic stroke patients.Methods and Results:A total of 2000 stroke patients were recruited during 2000-2001 and prospectively followed up for a median of 4.5 years. The independent association of a low eGFR with stroke recurrence and poor prognosis was evaluated using Kaplan-Meier analysis and Cox regression models. Among the overall stroke patients, the incidence rate of a low eGFR for the compound endpoints (stroke recurrence, myocardial infarction, and all-cause mortality) was greater than that of a normal eGFR (P0.001). A similar result was observed for the incidence rate of recurrence and death caused by cardiovascular disease or stroke (Csdeath) (P=0.009, and P=0.001, respectively). After adjustment for age, sex, and other cardiovascular risk factors, a low eGFR was associated with a 1.93-fold increased risk of the compound endpoints (P<0.001, RR=1.93,95% CI=1.39-2.69),1.62-fold increased risk of recurrent stroke (P=0.024, RR=1.62,95% CI=1.07-2.47), and 1.96-fold increased risk of Csdeath (P=0.022, RR=1.96,95% CI=1.10-3.49) among overall stroke patients. Among the hemorrhagic stroke patients, the incidence rate of a low eGFR for the compound endpoints (stroke recurrence, myocardial infarction, and all-cause mortality) was greater than that of a normal eGFR (P=0.012). A similar result was observed for the incidence rate of recurrence and death caused by cardiovascular disease or stroke (Csdeath) (P=0.013, and P=0.001, respectively). After adjustment for age, sex, and other cardiovascular risk factors, a low eGFR was associated with a 2.93-fold increased risk of the compound endpoints (P=0.001, RR=2.93,95% CI=1.58-5.43),3.06-fold increased risk of recurrent stroke (P=0.003, RR=3.06,95% CI=1.46-6.40), and 3.57-fold increased risk of Csdeath (P=0.005, RR=3.57,95% CI=1.46-8.70) among hemorrhagic stroke patients.Conclusions:Among the overall stroke and hemorrhagic stroke patients, a low eGFR was a strong predictor of stroke recurrence and a poor prognosis.