Grant: Project Grant

Muscular dystrophy is caused by mutations in key genes responsible for myofiber homeostasis. However, we have found the same genes expressed in the blood vessels that perfuse skeletal muscles, raising the hypothesis that deficient muscles in muscular dystrophy are perfused by deficient blood vessels, and that one can aggravate another. To test the interplay between blood vessels and muscular dystrophy, we took mice with muscular dystrophy and gave them a common blood vessel disease called atherosclerosis by altering their plasma lipid profile, what most people refer to as high cholesterol. To our surprise, these mice show drastically aggravated muscular dystrophy, up to the point of completely incapable of any locomotion mid-age, something never reported in mouse models of muscular dystrophy. Since it would be relatively easy to lower cholesterol in patients suffering from muscular dystrophy in an attempt to attenuate the inevitable rate of muscle function loss, we propose to shed a new light on plasma lipids and associated lipoproteins in muscle disease and show that improving lipid profiles attenuates muscular dystrophy in what we believe to be the most advanced pre-clinical model of MD.