Association Of Serum SIRT3 And Endocan Levels With Essential Hypertention And Target-organ Damage

Background:Essential hypertension(EH)is hazardous factor for cardiovascular diseases which remains an ever-increasing blood pressure with heterogenerous disorder and environmental interaction.Hypertension aggregates with target-organ damage such as left ventricular hypertention(LVH),carotid artery plaque and artery dysfunction,has drawn a great deal of attention in recent years.According to the ESH/ESC guideline in 2013,asymptomatic target-organ damage was defined as follows:Pulse pressure(in the elderly)>60 mmHg;echocardiographic LVH[LVM index,man>115g/m2,woman>95 g/m2(BSA)];Carotid wall thickening(IMT)?0.9mm or plaque;Carotid-femoral PWV>10m/s;Ankle-brachial index<0.9.LVH usually characterized by the increase of left ventricular wall thickness,with or without left ventricular cavity expansion.Hypertension patients with LVH are more easily occurred cardiac ischemia,arrhythmia or sudden death,which has been proved by evidence-based medical research that LVH are the independent risk factors of cardiovascular events.Meanwhile,carotid intima-media thickness and plaque are closely associated with cardiovascular events,which was taken as a window of assessment of the progress of systemic atherosclerosis.Pulse wave velocity(PWV)is one of the commonly used evaluation methods of vascular lesions providing information about arterial function.PWV is also an independent predictor of cardiovascular mortality.SIRT3,a sirtuin family members of nicotinamide adenine dinucleotide(NAD)+-dependent protein deacetylase,has received a great deal of attention in yeast.Previous study has established many functions for SIRT3 as critical regulator sensor at the crossroads between cell proliferation apoptosis,metabolism,genetic control of ageing,stress resistance and tumor-suppressive.Recent novel evidence suggests that SIRT3 may block heart hypertrophy by inhibiting lipid metabolism disordersHowever,the expression of serum SIRT3 in EH and target-organ damage remains unknown.Endocan,endothelial cell specific molecule 1(ESM1),one of the vascular endothelium molecules,has been shown to play a crucial role in inflammation,coagulation,angiogenesis,and tumor invasion.Indeed,various studies demonstrated that the relation between endocan and cardiovascular diseases,which associated with endothelial information,endothelial injury,activation,and dysfunction caused by oxidative stress.Thus,we considered that serum SIRT3 and endocan is possibly related to essential hypertension.However,no previous study has investigated serum SIRT3 and endocan levels in target-organ damage.Therefore,we evaluated the serum SIRT3,endocan levels in essential hypertension patients with and without target-organ damage and aimed to investigate the relationships of serum SIRT3,endocan levels between essential hypertension and target-organ damage.Objective:1.To explore the relationships between serum SIRT3/endocan and essential hypertension.2.To explore the relationships between serum SIRT3/endocan and target-organ damage.3.To assess whether serum SIRT3 and endocan be indicators in the development of the essential hypertension.Methods:A total of 132 patients attending to cardiology department outpatient of Qilu Hospital of Shandong University was enrolled in this study if they met the inclusion and exclusion criteria and submitted written informed consent.They were divided into three groups,essential hypertension(EH)with(n=58)or without target-organ damage(n=27)according to transthoracic echocardiography and carotid and the normotensive control(n=47).Hypertension was diagnosed as a systolic blood pressure(SBP)of?140 mmHg and/or a diastolic blood pressure(DBP)of>90 mmHg with repeated measurement.Target-organ damage was defined as left ventricular hypertrophy and/or carotid plaque.The pilot study which got approvement of local ethics committee was in compliance with the Helsinki Declaration.Drug history blood pressure,height,weight as well as other parameters were recorded.Enzyme-linked immuno-sorbent assay was applied to evaluate the serum level of SIRT3 and endocan.Transthoracic echocardiography,carotid ultrasound and Brachial-ankle pulse wave velocity were examed and related parameters were collected.Data were expressed as mean±SEM.Differences between groups were analyzed by one-way ANOVA followed by least significance difference(LSD)test or Dunnett T3 depend on variance homogeneity test.Covariance analysis is applied to evaluated serum SIRT3 and endocan levels additionally.Relations between SIRT3/endocan and other continuous variables were evaluated by partial correlation analysis.Relationships between variables were determined by simple linear regression analysis.Multiple linear regression analysis was applied to identify independent determinants of SIRT3 and endocan.Significance level was set at p<0.05.Statistical analysis was performed by SPSS 20.Results:1.Patients with or without target-organ damage showed no significant difference with control group in age,sex,BMI,Glucose,TG and BUN(P>0.05),but different in SBP,DBP,HDLC,LDLC and UA(P<0.05).2.Carotid ultrasonographic data showed that IMT,SC,BaPWV were significantly higher in target-organ damage group but DC and strain were significantly lower compared to non-target-organ damage and control group(P<0.05).3.Echocardiographic data showed that IVSd,LVIDd,LVPWTd,LVMI,Ds and Dd were significantly greater in target-organ damage group(P<0.05).4.Serum SIRT3 level was far lower in target-organ damage group but serum endocan level was significantly greater compared to non-target-organ damage group and control group.5.In all subjects,serum SIRT3 level showed significant negative correlations with BaPWV,carotid mean-IMT,LVMI,Strain(r=-0.473,P<0.001;r=-0.314,P<0.001;r=-0.331,P<0.001;r=-0.272,P<0.01),but serum endocan level showed positive correlations with BaPWV,carotid mean-IMT,LVMI,strain and plaque scores(r=0.188,P<0.05;r=0.219,P<0.05;r=0.233,P<0.05;r=0.22,P<0.05;r=0.192,P<0.05).6.Multiple linear regression analysis revealed that SIRT3 had significant independent association with BaPWV,mean-IMT,DC(?=-0.286,P=0.001;?=-0.21,P=0.011;p=-0.219,P=0.011).Conclusion:1.The lower expression of serum SIRT3 level in target-organ damage implicate that SIRT3 may play a role in preventing hypertension development.2.The increasing of serum endocan level in target-organ damage may represent the severity of the essential hypertension and target-organ damage and may present a new clinical therapy.