Characterization of the DMD mouse's dynamic skeletal muscle microvascular niche
Abstract
Duchenne muscular dystrophy (DMD) is a progressive muscular and microvascular degenerative disease affecting 1 in 3,500 boys. Chronic inflammation in skeletal muscle causes the onset of fibrosis caused by impaired angiogenesis and myogenesis. Improving angiogenic outcomes is a high priority. Previous studies have shown treatment with exogenous angiopoietin-1 (ANG1), a vascular stabilizing factor, reduced inflammation, ischemia, and fibrosis in animal models of DMD. This study further characterized DMD disease progression and the effects of exogenous ANG1 treatment had on the skeletal microvascular niche in DMD mice. The inflammatory and angiogenic response in mdx/utrn+/- mouse gastrocnemius samples were evaluated with immunohistochemistry and RT-qPCR. The microvascular niche lacked key gene and protein expression at 8 and 10 weeks of age. This had a cascading effect resulting in reduced myofiber size. Two weeks after ANG1 treatment some key microvascular niche gene expression and proteins had increased which led to increased myofiber size.