[Molecular determinants of pathological cardiac remodeling: the examples of Epac and Carabin].
Physical exercise or hypertension requires that the heart increases its hemodynamic work. However, this adaptation is based on distinct cardiac remodelling according to the physiological or pathological origin of the stress. As shown here with two examples, understanding the molecular events leading to cardiac remodeling may offer new opportunities for the development of therapies for heart failure. The recently described Epac1 protein is an effector of the second messenger cAMP. Following a pathological stress, the cAMP-binding protein Epac1 induces cardiac hypertrophy and fibrosis as well as alteration of calcium cycling suggesting that Epac1 pharmacological inhibition may be of therapeutic value. Furthermore, the protein carabin is an important regulator of several effectors of pathological cardiac remodelling. Experimental manipulation of carabin expression profoundly alters the development of heart failure.
Inserm, UMR-1048, institut des maladies métaboliques et cardiovasculaires, 1, avenue Jean Poulhès, BP 84225, F-31342 Toulouse Cedex 4, France - Université Toulouse III Paul Sabatier, F-31342 Toulouse, France - Faculté des sciences pharmaceutiques, Université Toulouse III Paul Sabatier, F-31342 Toulouse, France.
Yannis
Y
Sainte-Marie
Inserm, UMR-1048, institut des maladies métaboliques et cardiovasculaires, 1, avenue Jean Poulhès, BP 84225, F-31342 Toulouse Cedex 4, France - Université Toulouse III Paul Sabatier, F-31342 Toulouse, France.
Malik
M
Bisserier
Inserm, UMR-1048, institut des maladies métaboliques et cardiovasculaires, 1, avenue Jean Poulhès, BP 84225, F-31342 Toulouse Cedex 4, France - Université Toulouse III Paul Sabatier, F-31342 Toulouse, France.
Florence
F
Tortosa
Inserm, UMR-1048, institut des maladies métaboliques et cardiovasculaires, 1, avenue Jean Poulhès, BP 84225, F-31342 Toulouse Cedex 4, France - Université Toulouse III Paul Sabatier, F-31342 Toulouse, France.
Frank
F
Lezoualc'h
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D006332:Cardiomegaly / Q000235:genetics / Q000473:pathology; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000502:physiology*; D006333:Heart Failure / Q000235:genetics* / Q000473:pathology; D006801:Humans; D015398:Signal Transduction / Q000235:genetics; D020257:Ventricular Remodeling / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; C116122:RAPGEF3 protein, human; C517115:TBC1D10C protein, human