| Objective:Atherosclerosis is a chronic inflammation disease caused by multiple factors including genetic factors and environmental factors. Inflammation plays a pivotal role in atherosclerotic plaque formation and plaque instability. Targeted intervention in inflammation disorders would delay the process of plaque formation and disruption. Oncostatin (OSM) is one of the family members of interleukin-6, with various biological activity. OSM has been demonstrated to be involved in atherosclerotic plaque progression and plaque instability process. Based on analysis results of bioinformation, we founded that lncRNA AK054758is located in the upstream of OSM gene and their sequences are complementary. So we proposed our hypothesis that lncRNA AK054758may influence the expression of OSM and participate in inflammatory process of atherosclerosis. In our study, we aimed to explore the mechanism of lncRNA AK054758involved in the inflammation of atherosclerosis in vitro.Methods:To test our hypothesis, we performed qRT-PCR method to detect the mRNA levels of lncRNA AK054758after THP-1cells were treated with LPS or ox-LDL; and then, we use qRT-PCR and ELIS A to test the expression of inflammatory cytokines (IL-6, TNF-α and MCP-1) and target gene OSM after THP-1cells were transfected with siRNA which can knockdown lncRNA AK054758or plasmid which can overexpress lncRNA AK054758.Results:When THP-1cells were treated with different concentrations of LPS (0.1μg/ml,1μg/ml,10μg/ml) for24h, decreased expression of lncRNA AK054758were obversed in a dose-dependent manner. When THP-1cells were treated with Lps(10μg/ml) for24h, compared with the control group, the expression of lncRNA AK054758was reduced to0.38-fold (P<0.01). The expression of lncRNA AK054758were increased to1.57-fold(P<0.01) after THP-1cells were treated with oxLDL(100μg/ml) for60h. After we use RNAi to knockdown the lncRNA AK054758, the increased mRNA levels of IL-6(1.90-fold,P=0.001)and MCP-1(2.06-fold, P=0.002) were detected significantly. However, the mRNA levels of TNF-a had no significant change. Whereas the decreased mRNA level of IL-6(0.12-fold, P<0.001) and MCP-1(0.46-fold, P=0.001) were observed significantly after upregulation of lncRNA AK054758, the mRNA levels of TNF-α also had no significant change. Furthermore, the results of ELISA were according to the change of mRNA level. To identify the hypothesis that lncRNAAK054758affect the expression of predicted target gene OSM, we use qRT-PCR to detect mRNA level of OSM after downregulation and upregulation of lncRNAAK054758. We found that down regulation of lncRNAAK054758increased OSM mRNAlevel(3.01-fold,P<0.01) and overexpression of lncRNAAK054758had opposite effect (0.43-fold, P<0.01). It indicated that OSM maybe the target gene of lncRNAAK054758.Conclusion:Our study showed that lncRNA AK054758can inhibit atherosclerotic inflammation reaction and OSM maybe its target gene. We first discovered an anti-atherosclerosic lncRNA, providing new clues for clarifing the mechanism of atherosclerosis. Type III collagen plays an important role in activating platelets, forming thrombus, and maintaining the mechanical properties of arteries. This study aimed to test the hypothesis that genetic variants of COL3A1(gene encoding type III collagen) contribute to recurrence and prognosis of stroke. We investigated the associations of three variants (rs2138533, rs11887092, and rs1800255) in the COL3A1gene with stroke recurrence and prognosis in1544patients with three subtypes of stroke:lacunar infarction (n=442), atherothrombotic infarction (n=670), and hemorrhage (n=432). These associations were evaluated by Kaplan-Meier analysis and Cox regression models. Patients were followed up for4.5years. The A allele of rs1800255in the COL3A1gene coding region was significantly associated with a reduced risk of stroke recurrence in patients with lacunar infarction (adjusted hazard ratio [HR]0.58,95%confidence interval [CI]0.36-0.93, P=0.024), but there was an increased risk of all-cause mortality of atherothrombotic patients (adjusted HR1.43,95%CI1.01-2.00, P=0.044). The TT genotype of rs2138533showed a significantly increased risk of death caused by cardiovascular disease or stroke in lacunar infarct patients (adjusted HR2.98,95%CI1.27-6.98, P=0.012), but there was a reduced risk of all-cause mortality for patients with intracerebral hemorrhage (adjusted HR0.34,95%CI0.12-0.93, P=0.036). The G allele of rs11887092increased the risk of stroke recurrence in patients with atherothrombotic stroke (adjusted HR1.59,95%CI1.04-2.44, P=0.035). In conclusion, variants of COL3A1might play a vital role in determining the risk of recurrence and prognosis after stroke. |
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