Shedding of proangiogenic microvesicles from hypertrophic scar myofibroblasts

Abstract

Hypertrophic scars are a common complication of burn injuries and represent a major challenge in terms of prevention and treatment. These scars are characterized by a supraphysiological vascular density and by the presence of pathological myofibroblasts (Hmyos) displaying a low apoptosis propensity. However, the nature of the association between these two hallmarks of hypertrophic scarring remains largely unexplored. Here, we show that Hmyos produce signalling entities known as microvesicles that significantly increase the three cellular processes underlying blood vessel formation: endothelial cell proliferation, migration and assembly into capillarylike structures. The release of microvesicles from Hmyos was dose-dependently induced by the serum protein α-2-macroglobulin. Using flow cytometry, we revealed the presence of the α-2-macroglobulin receptor-low-density lipoprotein receptorrelated protein 1-on the surface of Hmyos. The inhibition of the binding of α-2macroglobulin to its receptor abolished the shedding of proangiogenic microvesicles from Hmyos. These findings suggest that the production of microvesicles by Hmyos contributes to the excessive vascularization of hypertrophic scars. α-2-Macroglobulin modulates the release of these microvesicles through interaction with low-density lipoprotein receptor-related protein 1.

More than just bricks and mortar: Fibroblasts and ECM in skin health and disease

“…Communication via micro‐vesicles is also a feature of myofibroblasts. In this issue, Laberge et al 53 report that myofibroblasts derived from human hypertrophic scars shed proangiogenic micro‐vesicles that significantly stimulate proliferation and migration by cultured endothelial cells and promote capillary‐like tube formation.…”

Preparation of Compound Salvia miltiorrhiza–Blumea balsamifera Nanoemulsion Gel and Its Effect on Hypertrophic Scars in the Rabbit Ear Model

“…Numerous studies have shown that the degree of scar hyperplasia is closely related to the growth of new blood vessels. , The microcirculation blood flow visualizer and immunohistochemical staining were used to investigate the effect of CSB-NEG on microcirculation of HS tissues. As shown in Figure C, microvessels in the normal skin tissue were clearly visible, with good blood circulation, and no abnormal proliferation of small vessels was observed.…”

“…TGF-β 1 mainly acts through the TGF-β/Smad signaling pathway. Research showed that the expression of TGF-β 1 , Smad2, and Smad3 increased in the scar tissue S.…”

“…Research showed that the expression of TGF-β 1 , Smad2, and Smad3 increased in the scar tissue. 64 S. miltiorrhiza has the capability to modulate the TGFβ/Smad pathway and exhibit antifibrotic effects by reducing the expression of TGF-β 1 and Smad2. 25,33,83 Both C. semen and P. rhizoma demonstrated inhibitory effects on the expression of TGF-β 1 .…”

Granulation tissue myofibroblasts during normal and pathological skin healing: The interaction between their secretome and the microenvironment

“…88 Another study reported the down-regulation of IL-6, IL-8 and CCL2 but an up-regulation of TNFα and CXCL4 with an augmented presence of M2 macrophages in the scar. 89 Laberge et al 90 have demonstrated that myofibroblasts isolated from hypertrophic scars produce microvesicles that stimulate angiogenesis, sustaining and further amplifying angiogenesis in these pathological scars. Further analysis would thus be necessary to evaluate whether inflammatory and pro-angiogenic mediators influence hypertrophic scarring in the skin in relation to myofibroblast persistence.…”