Relationship Between MiRNA-29a And Left Ventricular Hypertrophy In Hypertension

ObjectivePrevious studies have shown that plasma miRNA-29a is associated with myocardial fibrosis and the degree of cardiac hypertrophy in patients with hypertrophic cardiomyopathy.However,the relationship between plasma miRNA-29a and left ventricular hypertrophy(LVH)in hypertension has not yet been reported.Therefore the purpose of this study is to investigate the relationship between the miRNA-29a and LVH in hypertensive patients and experimental hypertensive LVH model.Methods1.The plasma miRNA-29a expression level in patients with hypertension.We enrolled 168 hypertensive patients.Collect the general clinical data,and echocardiographic examination was conducted.Relevant parameters of LVH were recorded including interventricular septal thickness(IVSd),left ventricular posterior wall thickness(LVPWTd),left ventricular end diastolic dimension(LVEDD),left ventricular end systolic diameter(LVESD),left ventricular end diastolic volume(LVEDV),left ventricular end systolic volume(LVESV),left atrium(LA),right atrium(RA),right ventricular(RV)left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS).And calculate left ventricular mass(LVM)and left ventricular mass index(LVMI).All patients with high blood pressure can be divided into two groups according to the results of the LVMI.One is hypertension with LVH(abbreviation for LVH group,n=41),another is hypertension without LVH(abbreviation for NLVH group,n=127).Blood samples were collected and the expressions of miRNA-29a in plasma were determined by real-time PCR(RT-PCR).Pearson correlation analysis was used to analyze the relationship between miRNA-29a and LVH related parameters.Multivariate linear regression was used to analyze the relationship between mirna-29a expression and IVSd,LVPWTd,LVEDD,LVESD,LVEDV,LVESV,LA,RA,RV,LVEF,LVFS and LVMI while Traditional risk factors for hypertension[gender,age,systolic blood pressure(SBP),diastolic blood pressure(DBP),body mass index(BMI),duration of hypertension,antihypertensive drugs,etc.]were excluded.2.The expression of miRNA-29a in myocardium in experimental hypertensive LVHanimal model.1)Chronic LVH model in hypertensionMicroosmotic pump was implanted subcutaneously in wild-type C57BL/6 mice(male)at 8 weeks of age.The experimental group(n=7)was subcutaneously pumped with 100ul angiotensin ?(Ang?),which was perfusion at the rate of 1.4ug/(kg?min)for 14 days continuously.The control group(n=8)was subcutaneously pumped with 100ul normal saline,which was perfusion for 14 days continuously.Changes in blood pressure and echocardiography were observed.After 14 days,sacrifice the mice,isolate the left ventricular tissue,and measuring the RNA expression of atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP)and miRNA-29a.2)Acute LVH model in hypertensionWe divided the wild-type C57BL/6 mice(male)at 8 weeks of age into two groups.The mice in the experimental group(n=10)underwent surgery of transverse aortic constriction(TAC)by partial ligation of the aortic arch results in aortic stenosis.In the SHAM group(n=10),no ligation was performed after the aortic arch was dissociated.The echocardiography were observed.After 14 days,sacrifice the mice,isolate the left ventricular tissue,and measuring the RNA expression of atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP)and miRNA-29a.Results1.Plasma miRNA-29a expression in patients with hypertensionPlasma miRNA-29a was significantly higher in hypertensive patients with hypertension LVH than those with NLVH(0.52±0.10 vs 0.37±0.07,P<0.01).3 days later,the blood pressure stars to go up.We found a positive correlation between plasma miRNA-29a levels and LVMI(R=0.745,P<0.01),IVSd(R=0.459,P<0.01),LVPWTd(R=0.398,P<0.01),LVEDD(R=0.345,P<0.01),LVEDV(R=0.302,P<0.01),LVESV(R=0.243,P<0.01)by using Pearson correlation analysis.Further analyzed by multiple linear regression,the positive correlations also remained between plasma miRNA-29a levels and LVMI(R=0.745,P<0.01),IVSd(R=0.459,P<0.01),LVPWTd(R=0.398,P<0.01),LVEDD(R=0.345,P<0.01),LVEDV(R=0.302,P<0.01)and LVESV(R=0.243,P<0.01)after adjustment for gender,age,SBP,DBP,BMI,hypertension duration,antihypertensive drugs.2.The experimental hypertensive LVH animal model1)Chronic LVH model in hypertensionCompared with control group,the SBP(108.8±7.4 vs 94.7±8.1,P<0.05)and DBP(84.8±3.4 vs 64±2,P<0.01)of mice in the Ang? group was significantly increased.And the echocardiography parameters of IVSd(1.73±0.17 vs 0.62±0.03,P<0.01),LVPWd(0.78±0.06 vs 0.71 ±0.01,P<0.01),and left ventricular mass versus body weight(LVM/BW)(3.41±0.05 vs 2.83±0.30,P<0.05)went up after 14 days.Anatomy of the mice,found that Ang ? group heart volume increased significantly than control group in mice.The HW/BW(3.98±0.16 vs 3.19±0.14,P<0.05)also increased.The expression of ANP(6.98±5.25 vs 1.06±0.06,P<0.01),BNP(5.41 ±0.28 vs 0.9±0.06,P<0.01)and miRNA-29a(1.16±0.19 vs 0.81 ±0.13,P<0.01)were higher than that of control group.2)Acute LVH model in hypertensionCompared with SHAM group,the echocardiography parameters of IVSd(1.04±0.21 vs 0.66±0.02,P<0.05),LVPWd(1.74±0.27 vs 0.76±0.11,P<0.01),and LVM/BW(4.29±1.11 vs 3.2±0.38,P<0.05)went up after 14 days.Anatomy of the mice,found that Ang II group heart volume increased significantly than control group in mice.The HW/BW(5.21±0.28 vs 4.59±0.24,P<0.05)also increased.The expression of ANP(1.36±0.12 vs 0.82±0.34,P<0.01),BNP(2.63±0.94 vs 0.74±0.24,P<0.01)and miRNA-29a(2.22±0.21 vs 0.89±0.47,P<0.01)were higher than that of control group.Conclusion1.The expression level of miRNA-29a is significantly higher in hypertensive patients with LVH than that with NLVH.And plasma miRNA-29a level is associated with LVH in hypertensive patients.2.The experimental hypertensive LVH animal model show that in chronic hypertension LVH caused by Ang ? and acute hypertensive LVH caused by TAC,the miRNA-29a expression in myocardial tissue was higher in mice of chronic and acute hypertensive LVH model than that of control.It showed that miRNA-29a participates in the regulation of hypertensive left ventricular hypertrophy.In the LVH group,myocardial fibrosis and hyperplasia were observed in animal models,and the apoptosis of myocardial cell increased.Our finding suggests that miRNA-29a may be involved in hypertensive LVH by regulation myocardial apoptosis.