Co-Authors:
Fromes, Y., UPMC, Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
Bouyon, S., UPMC, Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
Nagi, S., UPMC, Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
Roussel, V., UPMC, Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
Genin, O., Institute of Animal Sciences, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Levi, O., Institute of Animal Sciences, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Pines, M., Institute of Animal Sciences, Volcani Center, P.O. Box 6, Bet Dagan 50250, Israel
Abstract:
BACKGROUND: Heart injury, which results from various causes, leads to a common final pathway of pathological remodeling and fibrosis that causes heart failure. OBJECTIVES: To evaluated the efficacy of halofuginone in reducing fibrosis and improving cardiac function in the myopathic hamster strain CHF147 that develop a cardiomyopathy which evolves into heart failure with a major increase in fibrosis. METHODS: Echocardiography and surface ECG were assessed with and without halofuginone treatment. Cardiac biopsies were stained for collagen and immunostained for pSmad3, collagen triple-helix repeat containing 1 (cthrc1). Collagen α1(I) was evaluated by in situ hybridization. Myofibroblasts number was assessed by immunostaining for collagen cross-linking enzyme. RESULTS: Halofuginone treatment resulted in a major reduction in cardiac collagen and cthrc1 levels that was associated with prevention and deceleration of the impairment of left ventricular function. Halofuginone reduced the number of myofibroblasts and reduced the number of nuclei with pSmad3 downstream of the TGFβ signaling. CONCLUSIONS: Halofuginone that inhibited cardiac collagen synthesis and improved cardiac function meets the criteria for a potential novel antifibrotic therapy for patients with cardiac fibrosis of various etiologies.