Restoration of Contractile Function in Isolated Cardiomyocytes From Failing Human Hearts by Gene Transfer of SERCA2a

• DOI: 10.1161/01.cir.100.23.2308
• Publication Date: 2012-06-12T00:42:29Z
• Authors: Federica del Monte; Sian E. Harding; Ulrich Schmidt; Takashi Matsui; Zhao Bin Kang; G. William Dec; Judith K. Gwathmey; Anthony Rosenzweig; Roger J. Hajjar
• Keywords: Phospholamban; Human heart

Background —Failing human myocardium is characterized by abnormal relaxation, a deficient sarcoplasmic reticulum (SR) Ca 2+ uptake, and negative frequency response, which have all been related to deficiency in the SR ATPase (SERCA2a) pump. Methods Results —To test hypothesis that an increase SERCA2a could improve contractile function cardiomyocytes, we overexpressed ventricular myocytes from 10 patients with end-stage heart failure examined intracellular handling function. Overexpression of resulted both protein expression pump activity induced faster contraction velocity (26.7±6.7% versus 16.6±2.7% shortening per second, P <0.005) enhanced relaxation (32.0±10.1% 15.1±2.4%, <0.005). Diastolic was decreased failing cardiomyocytes overexpressing (270±26 347±30 nmol/L, <0.005), whereas systolic increased (601±38 508±25 <0.05). In addition, response normalized SERCA2a. Conclusions —These results support premise gene-based therapies targeting specific pathways may offer new modality for treatment this disease.