Correlation Of Sema3A And NRP-1 With Diabetic Macrovascular Disease

Diabetic macrovascular disease has become the chronic complication with the highest incidence and fatality rate of diabetes in China.The main underlying pathological changes are endothelial cell damage,of which VEGF is the most known endothelial mitogen,and NRP-1 can be used as VEGF co-receptors affect endothelial cell function.In addition,NRP-1 ligand Sema3 A can affect endothelial cell remodeling and angiogenesis.Studies have confirmed that Sema3 A and NRP-1 are expressed in diabetic retinal endothelial cells,and high glucose is one of the factors that stimulate the expression of NRP-1 and inhibit the expression of Sema3 A.It can be speculated that NRP-1 and Sema3 A may play a role in diabetic macrovascular disease.In this experiment,the expression levels of Sema3 A and NRP-1 in human umbilical vein endothelial cells and the changes of endothelial cells in high glucose and high fat environment were tested in vitro,and the patients with diabetic macrovascular disease were compared.The expression levels of Sema3 A and related cytokines in serum of patients with simple diabetes and healthy individuals were analyzed to analyze the role of Sema3 A and NRP-1 in MCV,providing new ideas and new targets for the prevention and treatment of MCV.Objective:Cellular experiments were performed to observe the expression of Sema3 A and NRP-1 in human umbilical vein endothelial cells cultured under normal,high-sugar and high-lipid conditions.The expression level of Semaphorin 3A(Sema3A)in serum of patients with diabetes mellitus complicated with carotid artery disease was analyzed to analyze the relationship between Sema3 A and Sema3 A.The relationship between carotid intima-media thickness(CIMT)in diabetic patients and the role of Sema3 A in diabetic macrovascular disease.Methods:1.Use an endothelial cell culture and take the cells from the 2nd to 4th passages for experimentation.Cells were cultured under normal,high-sugar,and high-lipid conditions,respectively.After 24 hours of culture,RT-PCR wasperformed to detect the expression of NRP-1 and Sema3 A mRNA.2.Select the experimental subjects: Select 116 patients with type 2 diabetes admitted to our department from January 2016 to May 2017.The diagnosis of diabetic patients meets the 1999 WHO diabetes standard;choose the same time in our hospital physical examination center In 57 healthy subjects,75 gaOGTT was performed to exclude diabetes,and carotid artery color Doppler ultrasound excluded carotid intimal lesions.In the subgroup,116 patients with type 2 diabetes were divided into 59 patients with normal CIMT(NCIMT)group,57 patients with CIMT thickening(ACIMT)group,and 57 healthy test subjects(NC).General information for statistical study subjects: age,sex,duration of illness,waist circumference(WC),hip circumference(HC),height,weight,body mass index(BMI),random blood pressure at admission.Clinical indicators: fasting plasma glucose(FPG),glycosylated hemoglobin(HbA1c),uric acid(UA),urea(UREA),creatinine(CRE),total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),serum Sema3 A.SPSS 20.0 software was used for statistical analysis of the above data,and to explore the relationship between the relevant indicators and diabetes with carotid artery disease.Results:1.Compared with the normal group,the expression of NRP-1 and Sema3 A mRNA in endothelial cells increased in high glucose and high lipid environment,and the difference was statistically significant(P<0.05).2.Compared with healthy subjects,the WC and FPG of diabetic patients increased,and CRE of NCIMT group decreased(P<0.05).Compared with ACIMT group,CRE of NCIMT group decreased(P<0.05).Logistic regression analysis showed that age and systolic blood pressure(SBP)were all related to thickening of CIMT.3.The serum Sema3 A levels in diabetic patients were higher than those in healthy individuals(P<0.01).Compared with NCIMT group,Sema3 A expression in ACIMT group was decreased(P<0.05).There was a negative correlationbetween serum Sema3 A and CIMT thickening(P<0.05).Conclusion:1.High glucose and high fat can increase the expression of NRP-1 and Sema3 A mRNA in HUVEC,which may be related to diabetic macrovascular disease.2.All of the subjects' serum Sema3 A was significantly positively correlated with hip circumference,fasting blood glucose and glycated hemoglobin.Obesity and abnormal glucose metabolism affected serum Sema3 A levels.3.Logistic regression analysis showed that low serum Sema3 A level is a protective factor for the development of diabetic macrovascular disease,and Sema3 A may play a protective role in the progression of atherosclerosis.