Key result
Local administration of Ang 1 in DMD mice attenuated angiogenesis, leading to fewer endothelial cells and more circular microvessels, while increasing expression of Vegfr1, Vegfr2, and Vegfa.
Why the study?
Chronic inflammation in Duchenne muscular dystrophy causes endothelial barrier dysfunction in skeletal muscle, prompting investigation into microvascular niche changes following local Ang 1 administration.
Does intramuscular injection of Angiopoietin 1 improve the gastrocnemius microvascular niche in a mouse model of Duchenne muscular dystrophy?
Does intramuscular injection of Angiopoietin 1 improve the gastrocnemius microvascular niche in a mouse model of Duchenne muscular dystrophy?
Exogenous Angiopoietin 1 attenuates dysregulated angiogenesis and increases essential gene expression in the skeletal muscle microvascular niche of a Duchenne muscular dystrophy mouse model.
Answers are grounded in this paper and cite their sources.
Angiopoietin-1 alters the microvascular niche in DMD mice; hypothesis-generating and leaves open any clinical translation.
Duchenne muscular dystrophy (DMD) is a degenerative neuromuscular disease caused by a lack of functional dystrophin. Ang 1 paracrine signalling maintains the endothelial barrier of blood vessels, preventing plasma leakage. Chronic inflammation, a consequence of DMD, causes endothelial barrier dysfunction in skeletal muscle. We aim to elucidate changes in the DMD mouse’s gastrocnemius microvascular niche following local administration of Ang 1. Gastrocnemii were collected from eight-week-old mdx/utrn+/− and healthy mice. Additional DMD cohort received an intramuscular injection of Ang 1 to gastrocnemius and contralateral control. Gastrocnemii were collected for analysis after two weeks. Using immunohistochemistry and real-time quantitative reverse transcription, we demonstrated an abundance of endothelial cells in DMD mouse’s gastrocnemius, but morphology and gene expression were altered. Myofiber perimeters were shorter in DMD mice. Following Ang 1 treatment, fewer endothelial cells were present, and microvessels were more circular. Vegfr1, Vegfr2, and Vegfa expression in Ang 1-treated gastronemii increased, while myofiber size distribution was consistent with vehicle-only gastrocnemii. These results suggest robust angiogenesis in DMD mice, but essential genes were underexpressed—furthermore, exogenous Ang 1 attenuated angiogenesis. Consequentially, gene expression increased. The impact must be investigated further, as Ang 1 therapy may be pivotal in restoring the skeletal muscle microvascular niche.
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McClennan et al. (2024) studied Duchenne muscular dystrophy (DMD). Angiopoietin 1 (Ang 1) vs. Contralateral control / vehicle-only was evaluated on Changes in the gastrocnemius microvascular niche (endothelial cells, morphology, gene expression). Local administration of Ang 1 in DMD mice attenuated angiogenesis, leading to fewer endothelial cells and more circular microvessels, while increasing expression of Vegfr1, Vegfr2, and Vegfa.
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