Calcium Cycling and Novel Therapeutic Approaches for Heart Failure

European Coordinator:
  • Anne-Marie LOMPRE, INSERM U621, Paris (France)
North American Coordinator:
  • Andrew MARKS, Columbia University, New York (USA)
  • Roger HAJJAR, Mount Sinai School of Medicine, New York (USA)
  • Sian HARDING, Imperial College, London (UK)
  • Evangelia KRANIAS, University of Cincinnati (USA)/Biomedical Research Foundation, Athens (Greece)
  • Martin LOHSE, University of Wurzburg (Germany)
  • Philippe CHARRON, INSERM U621, Paris (France)
  • Gerald W. DORN II, University of Cincinnati (USA)
  • Stefan ENGELHARDT, University of Wuezburg (Germany)
  • Alain LACAMPAGNE, INSERM U637, Montpellier (France)
  • Stephan LEHNART, Georg August University Medical Center, Goettingen (Germany)
  • Frederica del MONTE, Harvard Medical School, Massachusetts General Hospital, Boston (USA)
  • Philip POOLE-WILSON, Imperial College, London (UK)
  • Cesare TERRACCIANO, Imperial College, London (UK)
  • Guy VASSORT, INSERM U637, Montpellier (France)
  • Eric VILLARD, INSERM U621, Paris (France)
  • Xander WEHRENS, Columbia University, New York (USA)
  • Magdi YACOUB, Imperial College, London (UK)

Heart failure can be an outcome of different cardiovascular disease processes. It continues to be an important source of death and disability from cardiac causes. While there are medications for heart failure which can improve survival, there are none currently which halt the progression of the disease. Ultimately heart failure is a diminished capacity of the heart to pump blood, the result of a problem at the level of the heart muscle.  This problem can be defined at the cellular level as a reduction in the ability of the heart cell to contract. Within the cell the regulation of calcium is vital to the process that translates the electrical signal coordinating a heart beat into an effective muscular contraction. This transatlantic network proposes to take up the study of how heart failure may be related to changes in the regulation of intracellular calcium. Particularly targeted for research are the pumps of the sarcoplasmic reticulum, which allow of the release and sequestration of calcium, in turn associated with muscle contraction and relaxation.

The network formed for this project will allow for a comprehensive examination of the role of calcium in heart failure. The various research centers comprising the network specialize in different aspects of the calcium cycle. Further, the view is to be more expansive than the role of calcium in the cell.  Changes in calcium regulation are known to cause changes in the expression of genes in the heart, which are implicated in harmful structural changes to the heart called “remodeling.” Based on previous research, certain members of the network are prepared to begin a gene therapy trial which targets SERCA2a, a calcium pumping mechanism in the heart cell. They plan to investigate how improvements in calcium regulation in turn affect the expression of genes and composition of proteins in the cell. It is hoped that the information gained through these studies will allow for the development of novel treatments for heart failure based upon the modification of calcium regulation in the heart cell.