The Correlation And Mechanism Of RBP4 And Essential Hypertension

Background:The prevalence of cardiovascular disease risk factors in China is obvious,leading to an increase in the number of cardiovascular diseases.As a common cardiovascular disease,hypertension is the leading cause of death and other cardiovascular diseases worldwide.However,hypertension can be prevented and controlled.Antihypertensive therapy can reduce the risk of heart failure by more than 50%,reduce the risk of stroke by 35%-40%,and reduce the risk of myocardial infarction by 20%-25%.Therefore,the guidelines for the recommendation of hypertension in our country should start with the control of risk factors,early diagnosis and treatment,and standardized management of patients,strengthen health education,and continuously improve the awareness rate,treatment rate and control rate,while actively controlling complications and prevention the target organ damage.One of the important pathological changes in hypertension is left ventricular hypertrophy.Left ventricular hypertrophy is a compensatory response of the heart to hemodynamic overload and neurohumoral stimuli.Even in the early stages,it is a harmful reaction that increases the incidence and mortality of cardiovascular disease.It is a malignant arrhythmia and cardiogenic.An independent risk factor for sudden death.Sustained cardiac hypertrophy changes the expression of certain proteins in cardiomyocytes,increases cardiomyocyte apoptosis and death,and the deterioration of cardiac function eventually develops into decompensated heart failure.Plasma retinol-binding protein(RBP4)is an adipokines and inflammatory factor secreted mainly by hepatocytes and adipocytes,and occurs with insulin resistance,diabetes,coronary heart disease,heart failure and hypertension.Development is closely related.Previous studies by our group have shown that the adipokines RBP4,as a new pro-inflammatory factor,may play a key regulatory role in the vicious circle of insulin resistance-pathological cardiac hypertrophy.Plasma RBP4 levels in animal mice are positively correlated with the development of systolic and diastolic blood pressure in essential hypertension.However,the relationship between systolic and diastolic blood pressure and plasma RBP4 in patients with essential hypertension is still unclear,and the relationship between the development of left ventricular hypertrophy and RBP4 in patients with essential hypertension has rarely been reported,and RBP4 affects the primary.The specific molecular mechanism of hypertension is worthy of further investigation.In order to investigate the correlation and mechanism of RBP4 and left ventricular hypertrophy and related markers in patients with essential hypertension,we have made specific relevant content.Objectives:1.Identify the correlation between plasma RBP4 and patients with essential hypertension;2.To study the correlation between plasma RBP4 and left ventricular hypertrophy and related markers in patients with essential hypertension;3.To explore the mechanism of RBP4 activation of RAS system in white adipocytes.Methods:1.From December 2016 to March 2019,in the Department of Cardiology,Second Affiliated Hospital of Nanjing Medical University,216 patients with primary hypertension who were not taking any antihypertensive drugs,96 patients of whom were enrolled.According to the level of blood pressure measured and the relevant diagnostic criteria of the Guidelines for Prevention and Treatment of Hypertension in China(Revised Edition of 2018),it is divided into hypertension group 1(n=45)and hypertension group 2(n=33).)and hypertension group 3(n=18),and included in the health check-up group as a control group(n=64).Measure height,weight,blood cholesterol,triglyceride,low-density lipoprotein,high-density lipoprotein,fasting blood glucose,fasting insulin,RBP4,etc.,and calculate changes in BMI?HOMA-IR and other indicators.At the same time,left ventricular mass index(LVMI)and relative wall thickness(RWT)calculated by echocardiography were classified into normal(N)group,concentric remodeling(CR)group(n=49),concentric hypertrophy(CL)group(n=21)and eccentric hypertrophy(EL)group(n=9)according to 2018 ESH /ESC hypertension management guidelines.2.Construction of recombinant RBP4 virus,mouse primary white fat cells were extracted and cultured,and mature white fat cells were treated with 24-well plate.Each group was n=6.The experimental group was divided into 5 groups,which were Control group 1(before differentiation and maturation of white adipocytes),Control group 2(no drug stimulation),RBP4 group(50 ?g/ml RBP4 stimulation for 48 h),TAK242 group(3 ?M TAK242 stimulation for 48 h),TAK242 + RBP4 group(pre-administered with 4 ?M TAK242 for 6 h,50 ?g/ml RBP4 was added)Stimulate 48 h).The supernatant of each group was collected and centrifuged to verify the expression levels of angiotensin II.The total RNA was extracted from the cells,and real-time quantitative RT-PCR was used to detect the differentiation and maturation of the relevant white mature adipocytes and the m RNA level of the RAS system activation pathway.Results:1.There was no significant difference in age,TC,LDL and creatinine between the EH group and the HC group(p>0.05).There were statistical differences in BMI,FBG,TG,HDL,LVDd,IVS,LVPW,SBP,DBP and MAP.Academic significance(p<0.05).2.RBP4 in the primary hypertension(EH)group was higher than the healthy control group(HC)(p < 0.05).3.The specificity and sensitivity of RBP4 in essential hypertension(EH)were 86.7% or 64.5%,respectively.4.RBP4 was a risk factor for hypertension(OR>1,p<0.05);And the risk of hypertension in patients with RBP4?33.1679 mg/l is 7.906 times higher than that in patients with RBP4<33.1679 mg/l.5.RBP4 was correlated with the blood pressure level of hypertension patients,especially for women younger than 40 years old.6.The expression level of RBP4 in CR group,CL group and EL group was ignificantly higher than that in normal control group(p< 0.05).7.In the white adipocyte experiment,high expression of RBP4 can activate the expression level of RAS-related m RNA and the expression of angiotensin II in the cell supernatant,and the RAS system-related m RNA after RBP4 downstream pathway is inhibited.Expression levels of angiotensin II was decreased in the cell supernatant.Conclusions:1.Plasma RBP4 levels are positively correlated with blood pressure levels in patients with essential hypertension.2.Plasma RBP4 is closely related to LVH in patients with essential hypertension.3.Plasma RBP4 may promote cardiomyocyte hypertrophy and myocardial fibrosis through inflammatory reaction,causing ventricular remodeling.4.Plasma RBP4 may promote blood pressure elevation by activating the RAS system.