1, MicroRNA And Vascular Smooth Muscle Apoptosis In Hypertensive Intracerebral Hemorrhage 2, MicroRNA-146a Single Nucleotide Polymorphism Rs2910164 Locus And The Occurrence And Prognosis Of Ischemic Stroke In China

Objective:Cardiac and cerebral vascular diseases has become the largest cause of death in China, stroke can lead to significant health’s burdens. Hypertensive intracerebral hemorrhage (HICH) is a sinister subtype of stroke. Once the HICH happen, there is not ideal to cope with diseases with better treatments and the prognosis is poor. Therefore, it is of great significance to study the mechanism of vascular lesions in HICH. It dues to various factors which cause blood pressure increases, result in bleeding from a ruptured blood vessel lesions in the brain. The present study is generally believed that the pathological changes of cerebral hemorrhage blood vessels including:millet sample microaneurysm, fibrinoid necrosis, however these mechanisms have not been able to fully explain the pathological changes of the blood vessels. Vascular smooth muscle is an important part of the blood vessels, vascular smooth muscle in ischemic stroke (increase) and hemorrhagic stroke (quantity reduced or even disappear) showed different characteristics. Studying the pathological changes of the vascular smooth muscle is important to explore pathological changes of the hypertensive cerebral hemorrhage. This study aims to establish HICH model in mice, and explore the pathological changes of vascular smooth muscle cells (apoptosis, autophagy, phenotype transformation, aging) in HICH, hence our study provides clues for the prevention of HICH.Methods:In C57BL/6 mice, hypertensive cerebral hemorrhage was induced with angiotensin II and L-NAME (N-nitro -L-arginine methyl ester) infusion. The brain tissue of the mice was taken immediately after it was euthanized and cerebral hemorrhage were identified by HE staining. The mice brain of cerebral hemorrhage group and the control group was identified by pathological change such as apoptosis, autophagy, phenotypic transformation and senescence.Results:Apoptosis is the mainly pathological change of HICH. The percentage of apoptosis of cerebral vascular smooth muscle cells in hypertensive cerebral hemorrhage was higher than that in normal group (6.82% vs.2.70%, P=0.002).Conclusions:Apoptosis of vascular smooth muscle cells may be one of the most imperative pathological changes in hypertensive cerebral hemorrhage.Object:Stroke is an important cardiovascular and cerebrovascular diseases with a high incidence, morbidity, and mortality.Hypertensiveintracerebral hemorrhage(HICH) is a dangerous subtype of stroke and is influenced by environmental and genetic factors. MicroRNAs(miRNA) play an vital role in gene regulation. Therefore, their potential in disease diagnosis and treatment are also very critical. Our study is investigated to identify stroke specific miRNAs and signal pathway through miRNAs microarray in HICH mice model perihematoma.Method:Our study collected 2 cases of HICH mice perihematoma tissue and brain tissue in control group separately. Firstly, selecting differentially expressed miRNAs using miRNAs microarray (p< 0.05 was considered as significant).Secondly, using a bioinformatics method to predict the target genes of differentially expressed miRNAs, and signaling pathways was enriched by KEGG pathways. Finally, miRNA-mRNA network was established, thus, we identified the significant pathway and specific miRNAs associated with HICH.Result:The miRNAs microarray shows that 28 differentially expressed miRNAs were identified in the HICH mice compared with control group, of which,25 miRNAs were up-regulated, and 3 miRNAs were down-regulated. According to its target gene prediction and KEGG signaling pathway enrichment function, our study found six signaling pathway that may be associated with HICH:T cell receptor signaling pathway, Wnt signaling pathway, Rapl signaling pathway, Sphingolipid signaling pathway, Ras signaling pathway, ErbB signaling pathway. According to the selected signaling pathway and miRNA-gene network, we predictd the specific miRNAs:mmu-miR-702-3p, mmu-miR-664-5p, mmu-miR-669e-5p, mmu-miR-297a-3p, mmu-miR-421-3p, mmu-miR-3475-3p, mmu-miR-491-5p, mmu-miR-466h-5p and mmu-miR-760-3p.Conclusion:The expressed miRNAs in the HICH group are different from those in control group.Obeject:Ischemic stroke is caused by both genetic and environmental factors, and so does its recurrence and prognosis.The single nucleotide polymorphism rs2910164 in microRNA (miR)-146a was found to be involved in a variety of diseases.We conducted a case-control study to investigate the association between the single nucleotide polymorphism rs2910164 in microRNA (miR)-146a and the risk of stroke incidence and prognosis.Methods:Our study is a large scale prospective study of a multi center. A total of 1139 ischemic stroke patients and 1585 age- and sex-matched control subjects were recruited. After a median follow-up period of 4.5 years, the end point of follow-up was the recurrence and death of stroke in patients with cardiovascular disease or stroke,1071 of these ischemic stroke patients were then recruited for a prospective study. In the case-control study, multivariate logistic regression analysis was used to evaluate associations between rs2910164 and stroke incidence. In the prospective study, we conducted Kaplan-Meier survival analysis and used Cox proportional hazards models to describe the association between rs2910164 and stroke recurrence and prognosis.Results:Multivariate logistic regression analysis revealed that rs2910164 was not associated with ischemic stroke incidence (odds ratio (OR)=1.00; 95% confidence interval (CI)=0.80-1.24;p=0.985). Meta-analysis of our case-control study and three others in Asian populations also suggested that there was no relationship between rs2910164 and ischemic stroke incidence (OR=1.09; 95% CI=0.96-1.22;p=0.179) under the dominant model of inheritance. The significance of differences in long-term outcomes was examined by the log-rank test of the respective comparison groups. The prospective study showed that rs2910164 led to a 1.56-fold increased risk of stroke recurrence (hazard ratio (HR)=1.56; 95% CI=1.10-2.20; p=0.013) and a 2.13-fold increased risk of death caused by cardiovascular disease or stroke (HR=2.13; 95% CI=1.31-3.46; p=0.002). The independent association of rs2910164 with stroke prognosis was evaluated using Cox regression models.Conclusions:Therefore, rs2910164 appears to be a strong predictor of stroke prognosis but not of stroke incidence in Asian populations.