Vascular therapy for Duchenne muscular dystrophy (DMD)

Figures

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  Figure 1.. Dystrophin-glycoprotein complex (DGC). Dystrophin protein possesses a rod-shaped structure that links the intracellular cytoskeleton network to extracellular components of the dystrophin-glycoprotein complex (DGC), including dystroglycan and sarcoglycans. Aside from structural roles, the sarcoglycan subcomplex plays essential roles in signal transduction and mechanoprotection. The central mucin domain in α-dystroglycan is heavily O-glycosylated, which plays an important role in the protein function. Alteration of the dystrophin glycoprotein complex (DGC) can lead to myofiber degeneration with necrosis resulting in alteration of muscle hemostasis, including compensation of muscle regeneration and inflammation-mediated fibrosis, as the main pathophysiology in patients with Duchenne muscular dystrophy (DMD).

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  Figure 2.. Flowchart of angiogenic formation. The steps involved in the formation of blood vessels after the production of angiogenic factors are shown. Endothelial cell (EC) migration, activation, and proliferation lead to the tube and loop formation of blood vessels, making it more stabilized.

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  Figure 3.. The function of VEGF-A. Vascular endothelial growth factor A (VEGF-A) is the major mediator of vasculogenesis, angiogenesis, vasodilation via nitric oxide (NO) release, chemotaxis of macrophages and granulocytes, and survival of cells, including myogenic cells. Together, these VEGF-A-mediated effects promote regeneration of skeletal muscle.

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  Figure 4.. Mechanism of action of vascular endothelial growth factor. The mechanism of action of vascular endothelial growth factor, which functions through its affinity for different receptors and exerts significant effects on blood vessels and lymphatic vessels, is shown.

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  Figure 5.. Process of sprouting angiogenesis in blood vessels. (1) Angiogenesis occurs in areas of low oxygenation and induces the production of vascular endothelial growth factor (VEGF), which binds to VEGFR2 on the surface of endothelial cells (ECs) to induce angiogenesis. (2) VEGF-VEGFR2 signaling triggers EC sprouting, which in turn causes Notch-mediated lateral inhibition in adjacent cells by the tip cells. VEGF-VEGFR2 signaling promotes tip cell differentiation while inhibiting tip cell formation in adjacent cells via the Dll4-Notch signaling pathway, promoting stalk cell differentiation of adjacent cells. This Figure was created with BioRender.com.

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  Figure 6.. Flowchart of the production of nitric oxide (NO) for vasodilation. The steps in the production of NO leading to the vasodilation of blood vessels are shown. Meanwhile, different drugs and effect of NO are shown with their respective mechanisms of action.