Objective To investigate the mechanism by which lectin-like oxidized low density lipoprotein receptor-1(LOX-1)regulates hyperglycemic-induced myocardial fibroblast(CFs)fibrosis through the glycogen synthase kinase-3β(GSK-3β)/signal transducer and activator of transcription 3(STAT3)pathway.Methods CFs were isolated,cultured and identified.LOX-1 RNAi lentiviral vector was constructed and infected CFs.The experimental groups were as follows:Normal control(NC)group,High glucose(HG)group,LV-LOX-1,LV-Con group,Hypertonic(HPG)group.After LV-LOX-1 and LV-Con were infected with CFs,adding 25 mmol/L glucose to culture CFs for 24 h,they were denoted as HG+LV-LOX-1 group and HG+LV-Con group.Cells in HG+LV-LOX-1 group and HG+LV-Con group were treated with 10 μ mol/L SB216763 and 10 μ mol/L STATTIC for 24 h,respectively,and then they were recorded as HG+LV-LOX-1+SB216763 group,HG+LV-Con+SB216763 group,HG+LV-LOX-1+STATTIC group and HG+LV-Con+STATTIC group.CCK-8 was used to detect the activity of CFs,and the expression levels of mRAN and protein of LOX-1,collagen type I(COL-I),thioredoxin 5(TXNDC5),GSK-3β,STAT3,p-GSK-3β and p-STAT3 were detected by qRT-PCR and Western blot.Results CFs infected with LOX-1 RNAi lentiviral vector were obtained,which showed green under fluorescence microscopy.Compared with HG and HG+LV-Con groups,the mRNA expressions of LOX-1,COL-I and TXNDC5 were decreased in HG+LV-LOX-1 group(P<0.05).Compared with HG+LV-LOX-1 group,mRNA expressions of COL-I and TXNDC5 were decreased in HG+LV-LOX-1+SB216763 and HG+LV-LOX-1+STATTIC groups(P<0.05).Compared with HG and HG+LV-Con groups,p-GSK-3β protein expression was increased in HG+LV-LOX-1 group(P<0.05),while LOX-1,p-STAT3,COL-I,TXNDC5 protein expression was decreased in HG+LV-LOX-1 group(P<0.05).Compared with HG+LV-LOX-1 group,p-GSK-3β protein expression was increased in HG+LV-LOX-1+SB216763 group(P<0.05),while the protein expressions of p-STAT3,COL-I and TXNDC5 were decreased in HG+LV-LOX-1+SB216763 and HG+LV-LOX-1+STATTIC groups(P<0.05).Conclusion LOX-1,GSK-3β,STAT3,TXNDC5,and COL-I are involved in high glucose induced CFs fibrosis.LOX-1 promotes the expression of TXNDC5 and COL-I through GSK-3β/STAT3 pathway,and inhibition of LOX-1 can inhibit high glucose induced CFs fibrosis.

Objective: To investigate the relationship between dietary polyunsaturated fatty acid (PUFA) intake and blood lipid, C-reactive protein (CRP) and homocysteine (Hcy) in patients with acute ischemic stroke or transient ischemic attack (TIA). Methods: Patients with acute ischemic stroke or TIA were enrolled consecutively from Nanjing Stroke Registry Program. The total dietary PUFA intake level was assessed by the food semi-quantitative frequency questionnaire. Venous blood samples were collected in the morning of the day after admission to the hospital to detect the levels of serum total cholesterol, triacylglycerol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, Hcy, and CRP. According to the median level of total PUFA intake, the patients were divided into low PUFA group and high PUFA group. The relationship between PUFA intake and blood lipid, CRP and Hcy was analyzed by Spearman correlation analysis, and multiple linear regression analysis was used to determine the independent correlation. Results: A total of 170 patients (85.1%) with acute ischemic stroke and 31 patients with TIA (14.9%) were enrolled. Their age was 62.9±14.1 years, 143 were males (71.1%), and the median PUFA daily intake was 12.8 g (interquartile range: 8.05-17.5 g). Compared with the high PUFA group (n=100), patients in the low PUFA group (n=101) were older, serum high-density lipoprotein cholesterol levels were lower, and CRP and Hcy levels were higher. The above differences were statistically significant (all P<0.05). Spearman correlation analysis showed that total dietary PUFA intake was significantly negatively correlated with the serum CRP (r=-0.24, P=0.001) and Hcy (r=-0.17, P=0.013) levels, and there was no significant correlation with the blood lipid levels. Multiple linear regression analysis showed that CRP was significantly negatively correlated with PUFA intake after adjusting for confounding factors (B=-0.28, P=0.012). Conclusions Dietary PUFA intake in patients with acute ischemic stroke or TIA may affect blood metabolism index and oxidative stress index. It is necessary to adjust the dietary structure of patients with low PUFA intake to reduce the risk of stroke recurrence.