Plasma Soluble (Pro)renin Receptor Levels Increased In Heart Failure Patients With Renal Dysfunction

Background: Activate of the renin-angiotensin system is the major pathophysiological mechanism of heart failure.The(pro)renin–renin receptor [(P)RR] discovered as an important novel component of the renin–angiotensin system(RAS),widely expressed in various tissues including heart,kidney,brain and liver,is thought to regulate the tissue renin–angiotensin system(RAS)through the non-proteolytic activation of prorenin,on the other hand,(P)RR can induces intracellular signalling,such as MAPK-ERK1/2 pathway,independent of RAS and contribute to cell proliferation and up-regulated fibrosis gene expression.The full-length integral(P)RR is cleaved by furin to generate soluble(pro)renin receptor [s(P)RR],which is detected in plasma and urine.The s(P)RR is a candidate biomarker reflecting the status of the tissue RAS.Up to now,the researches have found s(P)RR levels can reflected the severity of some diseases.For example,renal lesion,gestational diabetes mellitus,gestational hypertension and obstructive sleep apnea syndrome.However,few data are available for evaluating the relationship between s(P)RR and heart failure.At present,whether s(P)RR levels are related to the severity of chronic heart failure,but the associations remain undetermined.Objectives: we study the chronic heart failure patients,discuss the relationship between plasma s(P)RR,renin concentration and clinical variables.Methods: A total of 61 patients with heart failure who were admitted to Heart internal medicine and 19 age-matched healthy subjects(HS)in the First Affiliated Hospital of Dalian Medical University from June 2015 to November 2015.The patients with heart failure were divided into two subgroups according to renal function(heart failure without renal dysfunction group[HF] and heart failure with renal dysfunction group,[HF+RF]).The history and general information of the patients were collected.Brain natriuretic peptide(BNP),serum creatinine(Scr),uric acid(UA),fasting plasma glucose(FPG),angiotensionI(AngI),angiotensionII(AngII),aldosterone(Ald),urine albumin-to-creatinine ratio(ACR)were measured.Peripheral venous blood sample about 5ml was collected and stored in EDTA tube.Plasma from each sample after centrifugation at 2000 for 15 minutes at low temperature centrifuger was extrated and stored at-80?for measurement.The plasma levels of s(P)RR and renin concentrations were evaluated by ELISA kits.All the patients received transthoracic echocardio-graphy(TTE),the left atrial diameter(LAD),left ventricular end-diastolic diameter(LVEDd),interven-tricular septum(IVS),left ventricular posterior wall thickness(LVPWT),mitral valve E peak deceleration time(EDT),E/e',left ventricular ejection fraction(LVEF),left ventricular mass index(LVMI)were obtained.Intima-media thickness(IMT)was measured by Carotid artery ultrasound.SPSS19.0 statistical software was applied to analysis the data.One-Way ANOVA or Chi-square test was used to analyze the difference between gourps.Pearson's correlation coefficient was used to assess the association between s(P)RR,renin and various clinical parameters.Multiple regression analysis was used to evaluate the independent determinants of s(P)RR,P-value<0.05 was considered to be statistically significant.Results:1.The plasma s(P)RR levels are 21.3±4.2ng/mL(HS),24.6±4.8 ng/ mL(HF),27.4±4.8ng/mL(HF+RF)in three groups patients,respectively.Compared to HS group,the plasma s(P)RR levels are significantly increased in HF group and HF+RF group(P<0.05?P<0.001).The plasma s(P)RR levels are significantly increased when HF+RF group compared to HF group(P<0.05).2.Heart failure patients(or with renal dysfunction),there was positive significant correlation between plasma s(P)RR levels and cardiac function assessed by New York Heart Association(NYHA)classification and LVMI(r=0.261,P=0.042;r=0.298,P=0.002.respectively).Plasma s(P)RR levels were significantly negative correlated with eGFR(r=?0.306,P=0.017).3.Plasma s(P)RR levels as dependent variable,BNP,eGFR,Ald,LVMI and NYHA classification as independent variables,multiple regression analysis shows that LVMI and eGFR were the independent determinant factors of s(P)RR.Conclusions: 1.Plasma s(P)RR levels were significantly higher in the chronic heart failure patients and in the chronic heart failure complicating with renal dysfunction patients,and more significantly increased in HF+RF group.2.In the chronic heart failure(or with renal dysfunction)patients,there was significant positive correlation between plasma s(P)RR levels and cardiac function assessed by NYHA classification and LVMI.Plasma s(P)RR levels were significantly negative correlated with eGFR.3.LVMI and eGFR were the independent determinant factors of the plasma s(P)RR levels.