Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 294, Issue 4, Pages H1550-H1561Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.01253.2007
Keywords
collagen I/III; echocardiography; Ki67; hepatocyte growth factor; alpha-smooth muscle actin
Ask authors/readers for more resources
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 alpha-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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available