Co-Authors:
Huebner, K.D., Department of Human Anatomy and Cell Science, Faculty of Medicine, University of Manitoba, MB, Canada
Jassal, D.S., Cardiac Sciences Department, Institute of Cardiovascular Sciences, University of Manitoba, MB, Canada
Halevy, O., Department of Animal Sciences, Faculty of Agriculture, Hebrew University of Jerusalem, Rehovot, Israel
Pines, M., Institute of Animal Sciences, Volcani Center, Bet-Dagan, Israel
Anderson, J.E., Department of Human Anatomy and Cell Science, Faculty of Medicine, University of Manitoba, MB, Canada, Department of Biological Sciences, Faculty of Science, University of Manitoba, MB, Canada, Dept. of Biological Sciences, Faculty of Science, Univ. of Manitoba, Dysart Rd., Winnipeg, MB R3T 2N2, Canada
Abstract:
The effect of halofuginone (Halo) on established fibrosis in older mdx dystrophic muscle was investigated. Mice (8 to 9 mo) treated with Halo (or saline in controls) for 5, 10, or 12 wk were assessed weekly for grip strength and voluntary running. Echocardiography was performed at 0, 5, and 10 wk. Respiratory function and exercise-induced muscle damage were tested. Heart, quadriceps, diaphragm, and tibialis anterior muscles were collected to study fibrosis, collagen I and III expression, collagen content using a novel collagenase-digestion method, and cell proliferation. Hepatocyte growth factor and α-smooth muscle actin proteins were assayed in quadriceps. Halo decreased fibrosis (diaphragm and quadriceps), collagen I and III expression, collagen protein, and smooth muscle actin content after 10 wk treatment. Muscle-cell proliferation increased at 5 wk, and hepatocyte growth factor increased by 10 wk treatment. Halo markedly improved both cardiac and respiratory function and reduced damage and improved recovery from exercise. The overall impact of established dystrophy and dysfunction in cardiac and skeletal muscles was reduced by Halo treatment. Marked improvements in vital-organ functions implicate Halo as a strong candidate drug to reduce morbidity and mortality in Duchenne muscular dystrophy. Copyright © 2008 the American Physiological Society.
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