Intracoronary sarcoplasmic reticulum calcium-atpase gene therapy in advanced heart failure patients with reduced ejection fraction: a prospective cohort study

OBJECTIVE: Heart failure is a progressive and debilitating disease. Intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy may improve the function of cardiac muscle cells. This study aimed to test the hypothesis that intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy can improve outcomes and reduce the number of recurrent and terminal events in advanced heart failure patients with reduced ejection fraction. METHODS: A total of 768 heart failure patients with reduced ejection fraction and New York Heart Association classification II to IV were included in this prospective cohort study. Patients either underwent intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy (CA group, n=384) or received oral placebo (PA group; n=384). Data regarding recurrent and terminal event(s), treatment-emergent adverse effects, and outcome measures were collected and analyzed. RESULTS: After a follow-up period of 18 months, intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy reduced the number of hospital admissions (p=0.001), ambulatory treatments (p=0.0004), and deaths (p=0.024). Additionally, intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy improved the left ventricular ejection fraction (p<0.0001) and Kansas City Cardiomyopathy Questionnaire score (p<0.0001). The number of recurrent and terminal events/patients were higher in the PA group than in the CA group after the follow-up period of 18 months (p=0.015). The effect of the intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy was independent of the confounding variables. No new arrhythmias were reported in the CA group. CONCLUSIONS: Intracoronary sarcoplasmic reticulum calcium-ATPase gene therapy reduces the number of recurrent and terminal events and improves the clinical course of advanced heart failure patients with reduced ejection fraction.

Bisoprolol increases myocardial SERCA2a activity in rats with heart failure / 基础医学与临床

Objective To investigate the effects of bisoprolol on myocardial SERCA2a activity in rats with heart fail-ure.Methods Male SD rats were randomly divided into normal control group (control group), sham operation group ( sham group ) , model group , bisoprolol group ( Bis group ) , captopril group ( Cap group ) and bisoprolol plus captopril group[(Bis+Cap)group], heart failure rat model was induced by intraperitoneal injections of doxorubicin .Distilled water, bisoprolol, captopril or bisoprolol plus captopril were administrated by gastrogavage for 35 days, respectively. Indices of cardiac function and plasma levels of B-type natriuretic peptide ( BNP) were measured , myocardial expres-sion of miR-25-3p was detected by Stem-loop RT-qPCR, myocardial levels of SERCA2a and phospholamban (PLB) were detected by Western blot , myocardial SERCA2a activity was determined by the inorganic phosphorus method . Results Cardiac function in model group decreased significantly while plasma levels of BNP were significantly higher than those of control group ( P<0.01 ) .Myocardial expression of miR-25-3p in model group was significantly higher while myocardial levels of SERCA 2a and PLB,SERCA2a activity were significantly lower than those of con-trol group(P<0.01).Cardiac function in Bis group , Cap group and Bis +Cap group improved significantly while plasma levels of BNP were significantly lower than those of model group ( P<0.01 ) .Myocardial expression of miR-25-3p in Bis group, Cap group and Bis +Cap group were significantly lower while myocardial levels of SERCA2a and PLB were significantly higher than those in model group (P<0.01).The SERCA2a/PLB ratio and SERCA2a activity in Bis group and Bis +Cap group were significantly higher than those of model group ( P<0.05 ) .Conclu-sions Bisoprolol therapy improves cardiac function in rats with heart failure , which may be related to inhibition of myocardial miR-25-3p, increasing myocardial SERCA2a and PLB levels, enhancing SERCA2a activity.

Effects of Xinkang recipe on myocardial miR-25-3p expression and SER-CA2 a activity in heart failure rats / 中国病理生理杂志

AIM:To investigate the effects of Xinkang recipe on myocardial miR-25-3p expression and sarco-plasmic reticulum calcium ATPase 2a ( SERCA2a) activity in heart failure rats .METHODS:Male SD rats were randomly divided into normal group , sham group , model group , Xinkang recipe group ( Xinkang group ) , and captopril group .The heart failure rat model was induced by intraperitoneal injection of doxorubicin .Distilled water , Xinkang recipe and capto-pril were administrated by gastric gavage for 35 d, respectively .The indexes of cardiac function and plasma level of brain natriuretic peptide (BNP) were measured.The SERCA2a activity was determined by the inorganic phosphorus method . The myocardial protein expression of SERCA 2a and phospholamban ( PLB) was detected by Western blot .The myocardial expression of miR-25-3p was detected by stem-loop RT-qPCR.RESULTS:Cardiac output (CO), left ventricular fraction-al shortening ( LVFS) and left ventricular ejection fraction ( LVEF) in Xinkang group and captopril group were significantly higher while the plasma levels of BNP were significantly lower than those in model group (P<0.01).The myocardial ex-pression levels of miR-25-3p in Xinkang group and captopril group were significantly lower while the myocardial protein le -vels of SERCA2a and PLB were significantly higher than those in model group (P<0.01).The SERCA2a/PLB ratio and SERCA2a activity in Xinkang group were significantly higher than those in model group (P<0.05), and no significant change was observed between captopril group and model group .CONCLUSION:Xinkang recipe therapy may improve car-diac function in heart failure rats , which may be related to inhibiting the expression of miR-25-3p, increasing the SER-CA2a/PLB ratio and enhancing SERCA 2a activity in the myocardium .