Adaptive and Maladaptive Signaling in Cardiac Growth and Regeneration

European Coordinator:
  • Helmut DREXLER († 13 September 2009)/Kai WOLLERT and Denise HILFIKER-KLEINER, Hannover Medical School (Germany)
North American Coordinator:
  • Jeffery D. MOLKENTIN, University of Cincinnati (USA)
  • Nanette H. BISHOPRIC, University of Miami (USA)
  • Victor J. DZAU, Duke University, Durham (USA)
  • Peter H. SUGDEN, University of Reading (UK)
  • Jean-Luc BALLIGAND, University of Louvain, Brussels (Belgium)

There is an inexorable progression to heart failure, making it a difficult and frustrating condition to treat. The molecular basis of this progression is not well understood, and hope for effective treatment lies in research into a way to interrupt the downward spiral of events that leads ultimately to incapacitation and death. Researchers in this transatlantic network hypothesize that the key to understanding the process of heart failure lies in paracrine signaling, the chemical messages that are produced by cells in the heart or stem cells and which direct changes in the heart’s structure or function. Some of the paracrine signaling pathways are already familiar to scientists, and figure into some of the most effective current treatments for heart failure. The goal of this project is to discover and characterize other important signaling molecules.

Recent research has shown that treatment of heart failure with bone marrow cells leads to improved function. The bone marrow cells do not, however, transform themselves into functioning heart cells. The network researchers hypothesize that the beneficial effects are secondary to paracrine signals that are elaborated by these cells; these signals are among those they hope to understand and characterize fully. In addition to identifying this kind of paracrine signal, the network will investigate how the signals are transduced, that is, processed into changes in the structure and function of the heart. This analysis will involve investigations at the genetic and proteomic levels. Investigators hope to be able to discover additional points of intervention in the process of heart failure, and thereby to propose new avenues for treatment.