The Association Between MicroRNA-92b And Cardiac Hypertrophy Hypertension-induced And The Mechanism

Chapter I Prevalence and Risk Factors of Left Ventricular Hypertrophy in essential Hypertension in CommunityBackground and aim:Left ventricular hypertrophy(LVH)is the most common target organ damage induced by hypertension.LVH is a strong predictor of myocardial infarction,sudden death,stroke,congestive heart failure,and overall mortality of cardiovascular disease.LVH subtype-classification could affect cardiovascular prognosis.In our study the latest definition of LVH was used to analyze the effective data of management network in community hypertensive patients.The aim of our study was to analyze the prevalence and risk factors of LVH and LVH subtypes among hypertensive subjects of Liaobu community in Dongguan.Methods:This retrospective analysis included 2290 hypertensive participants without other cardiovascular disease,valve disease and with ejection fraction>50%.The type of LV geometric abnormality was defined on the basis of the new classification system.Result:LVH was detected in 555 patients(24.2%).The concentric LVH was the most common LVH subtype(14.8%).Multivariate logistic regression analysis showed that the risk factors for LVH were systolic blood pressure(SBP)and age,and the protective factor was male.After adjustment for age,gender,body mass index(BMI),history of hypertension and alcohol consumption,stepwise regression analysis showed that compared with eccentric LVH,concentric LVH was associated with more risk factors.Age,neck circumference(NC),SBP,hyperuricemia and alcohol consumption were positively correlated with concentric LVH,while BMI and male were negatively correlated with concentric LVH.Alcohol consumption was the strongest risk factor associated with concentric LVH.Age and abdominal obesity were positively associated with eccentric and non-dilated LVH,whereas male were negatively correlated with eccentric and non-dilated LVH.Abdominal obesity is the most associated risk factor for eccentric and non-dilated LVH.SBP and age were positively correlated with eccentric and dilated LVH,while male was negatively correlated with eccentric and dilated LVH.Age is the most relative risk factor for eccentric and dilated LVH.Conclusion:Our study concluded that the prevalence of LVH in patients with hypertension was 24.2%.SBP,age and female were the risk factors of LVH.The concentric LVH was the most common LVH subtype.There were more risk factors associated with concentric LVH.Chapter ? Correlation between circulating miRNA-92b,miRNA-155 and left ventricular hypertrophy in essential hypertensive populationBackground and aim:MicroRNAs are small noncoding RNAs of 22 nucleotide single-stranded that are key posttranscriptional regulators of gene expression.A large number of studies showed that miRNAs not only play an important role in cardiovascular development,but also closely related to cardiac hypertrophy,myocardial fibrosis,cardiac remodeling,heart failure,myocardial infarction and other cardiovascular diseases.Due to the stability of miRNAs in circulating blood,miRNAs had been identified as biomarkers for a variety of cardiovascular diseases.In our study,qRT-PCR was used to verify the correlation between the level of miR-155,miR-92b and miR-133b and left ventricular hypertrophy in essential hypertensive population.Method:Each 40 patients with hypertensive left ventricular hypertrophy and hypertensive non-left ventricular hypertrophy were randomly selected from the database of community hypertensive patients.40 healthy subjects with matched age and sex selected from the community were collected the peripheral blood samples.The total RNA was extracted from the plasma by RNA extraction kit.The miR-155,miR-92b and miR-133b were detected by miRNA fluorescence quantitative detection kit through qRT-PCR.The U6 was used as the internal control.The relative expression levels of miR-155,miR-92b and miR-133b were calculated by the ?Ct method.The relative expression levels of miRs were analyzed through spearman correlation analysis,Logistic regression and ROC curve analysis.Result:Compared with healthy participants,the relative expression levels of miR-155 and miR-133b was up-regulated,whereas the relative expression levels of miR-92b was down-regulated.The relative expression levels of miR-155 and miR-92b was significantly correlated with LVMI and SBP.The relative expression level of miR-155 is a risk factor for LVMI.MiR-155 might play pro-hypertrophy role.The relative expression level of miR-92b is negatively associated with LVMI.MiR-92b might play anti-hypertrophy role.Conclusion:Our results suggest that miR-155 and miR-92b may be involved in the regulation of BP and LVH in hypertensive patients.They may be a therapeutic target for cardiac hypertrophy.However,their mechanisms need further research confirmed.Chapter ? The role and mechanism of miR-92b in angiotensin ?-induced cardiomyocyte hypertrophyBackground and aim:MiRs play important roles in the development and progression of cardiac hypertrophy.Recent studies found that the expressions of several miRs were decreased in cardiac hypertrophy.They may exert efforts of anti-cardiac hypertrophy.Our previous study demonstrated that miR-92b expression is down-regulated in circulating blood of patients with essential hypertension.In this study,we aim to examine the expression level of miR-92b in Ang II-induced cardiomyocyte hypertrophy,and identify whether it could inhibit cardiomyocyte hypertrophy.Method and Result:The expression of miR-92b in Ang-?-induced hypertrophic neonatal mouse ventricular cells(NMVCs)was significantly down-regulated.After miR-92b mimic was transfected into NMVCs,the expressions of ANP and ?-MHC were significantly decreased in Ang-? induced NMVCs.The luciferase reporter assay showed that GATA6 was the direct target gene of miR-92b.The expressions of ANP and P-MHC protein in NMVCs were significantly increased and the expression of GATA6 mRNA and protein was significantly up-regulated in Ang ?-induced cardiomyocyte hypertrophy.The expression level of GATA6 mRNA and protein was significantly down-regulated after transfection with GATA6 siRNA or miR-92b mimic.FITC-phalloidin staining showed that miR-92b mimic and GATA6 siRNA could attenuate the increase of NMVCs size Ang II-induced.The expressions of ANP,?-MHC and GATA6 was down-regulated by miR-92b mimic and GATA6 siRNA in Ang ?-treated NMVCs.Knockdown of P65 through transfection with NF-?B P65 siRNA could attenuate the down-regalation of miR-92b induced by Ang-? in NMVCs.QNZ,NF-?B inhibitor,could attenuate the down-regulation of miR-92b expression induced by Ang ?.Conclusion:Our study showed that miR-92b was down-regalated in cardiac hypertrophy induced by Ang ?.MiR-92b attenuated hypertrophic phenotype induced by Ang ? in neonatal mouse ventricular cells(NMVCs).MiR-92b inhibited cardiac hypertrophy by down-regulation of GATA6.Inhibition of NF-?B signaling pathway attenuates the decrease of miR-92b expression induced by Ang ?.Therefore,our study suggested that miR-92b may be a target for the prevention and treatment of cardiac hypertrophy.