Hyperactivity of fibroblasts and functional regression of endothelial cells contribute to microvessel occlusion in hypertrophic scarring

Wang, Xiqiao; Liu, Yingkai; Qing, Chun; Lu, Shuliang

doi:10.1016/j.mvr.2008.08.007

Cited by 38 publications

(30 citation statements)

References 44 publications

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“…Electron microscopy was employed as previously described to observe changes in the EC and fibroblast microstructures [7]. First, tissue samples were fixed with 2.5% glutaraldehyde followed by 1% OsO 4 .…”

Section: Methodsmentioning

confidence: 99%

“…In addition, the endothelium is regarded as a massive endocrine organ that releases many types of growth factors, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), transforming growth factor beta 1 (TGF-β1), and endothelin 1 (ET-1), thereby establishing the microenvironment [5–7]. Endothelium-derived growth factors are critical for regulating the development and maintenance of many organs, including the liver, pancreas, and nervous system [8–10].…”

Section: Introductionmentioning

confidence: 99%

“…Based on the results of our previous study, microvessel occlusion and functional EC regression occur prior to scar regression [7]. However, the roles of this process in inducing EC dysfunction and subsequent scar regression are understudied.…”

Section: Introductionmentioning

confidence: 99%

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Hypertrophic scar regression is linked to the occurrence of endothelial dysfunction

Wang¹,

Song²,

Liu³

2017

PLoS ONE

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Most microvessels have been shown to become stenosed or completely occluded during hypertrophic scar progression. Here, we examined the morphology of capillary endothelial cells (ECs) and fibroblasts using immunofluorescence staining for CD31 and alpha-smooth muscle actin (α-SMA) and electron microscopy. In addition, ECs and fibroblasts were isolated from scar tissues, and the levels of transforming growth factor beta 1 (TGF-β1), platelet-derived growth factor (PDGF), endothelin 1 (ET-1), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were assayed using ELISAs. Furthermore, we assessed cell viability, total collagen production, and cell apoptosis in hypertrophic scar-derived fibroblasts cultured with EC-conditioned medium. Then, anti-TGF-β1, anti-PDGF, anti-ET-1, anti-VEGF, and anti-bFGF neutralising antibodies were individually added to the EC medium to identify which growth factor plays a more important role in inhibiting fibroblasts biology. Our results showed microvessel lumen occlusion and EC atrophy during scar development, particularly in regressive scars (RSs). Additionally, EC growth factor secretion decreased and reached the lowest levels in RSs. Furthermore, based on the culture results, RS EC medium inhibited fibroblast viability and collagen production and induced apoptosis. Moreover, TGF-β1, PDGF, and bFGF played more important roles in these processes than VEGF and ET-1. The endothelial dysfunction occurring in hypertrophic scars contributes to fibroblast inhibition and scar regression, and reduced TGF-β1, PDGF, and bFGF levels play key roles during this process.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hypertrophic scar regression is linked to the occurrence of endothelial dysfunction

Wang¹,

Song²,

Liu³

2017

PLoS ONE

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“…The granulation tissue continues to grow due to the excessive secretion of growth factors and the lack of molecules required for apoptosis or ECM remodeling. Hypertrophic scars contain excessive microvessels, which are mostly occluded due to the overproliferation and functional regression of endothelial cells induced by myofibroblast hyperactivity and excessive collagen production [63]. …”

Section: Scarringmentioning

confidence: 99%

Wound Repair and Regeneration

2012

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The skin is the biggest organ of the human being and has many functions. Therefore, the healing of a skin wound displays an extraordinary mechanism of cascading cellular functions which is unique in nature. As healing and regeneration processes take place in all parts of the human body, this review focuses on the healing processes of the skin and highlights the classical wound healing phases. While regeneration describes the specific substitution of the tissue, i.e. the superficial epidermis, mucosa or fetal skin, skin repair displays an unspecific form of healing in which the wound heals by fibrosis and scar formation. The first stage of acute wound healing is dedicated to hemostasis and the formation of a provisional wound matrix, which occurs immediately after injury and is completed after some hours. Furthermore, this phase initiates the inflammatory process. The inflammatory phase of the wound healing cascade gets activated during the coagulation phase and can roughly be divided into an early phase with neutrophil recruitment and a late phase with the appearance and transformation of monocytes. In the phase of proliferation the main focus of the healing process lies in the recovering of the wound surface, the formation of granulation tissue and the restoration of the vascular network. Therefore, next to the immigration of local fibroblasts along the fibrin network and the beginning of reepithelialization from the wound edges, neovascularization and angiogenesis get activated by capillary sprouting. The formation of granulation tissue stops through apoptosis of the cells, characterizing a mature wound as avascular as well as acellular. During the maturation of the wound the components of the extracellular matrix undergo certain changes. The physiological endpoint of mammalian wound repair displays the formation of a scar, which is directly linked to the extent of the inflammatory process throughout wound healing.

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“…38 A study indicated that, the vascular caliber was larger in pathological scars; even with the increased blood flow in the tissue, blood supply doesn't actually reach the periphery; 13 and the ineffective oxygen exchange through vascular walls may still result in hypoxia.…”

Section: Correlation Of Blood Supply and Tissue Hypoxia In Pathologicmentioning

confidence: 99%

The Characteristics of Blood Supply and Tissue Hypoxia in Pathological Scars

李梓菲¹,

Li²,

刘清亮³

et al. 2017

Chinese Medical Sciences Journal

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Blood supply is believed to be an important aspect in the development of pathological scars. However, there are controversies about vascular distribution, vascular structure and blood flow in pathological scars. Additionally, hypoxic microenvironment plays an important role in the vascularization of pathological scar tissues, and hypoxic conditions can be reflected by metabolic indexes and some cytokines. Furthermore, the correlation between blood supply and tissue hypoxia is controversial. The aim of this article is to review the literature on the characteristics of blood supply and tissue hypoxia in pathological scars, from which we can see pathological scars have unique characteristics of blood supply that are closely associated with tissue hypoxia. Moreover, development in the treatment of pathological scars is herein reviewed.Chin Med Sci J 2017; 32(2):113-118. DOI:10.24920/J1001-9294.2017.014 ATHOLOGICAL scars include hypertrophic scar and keloid. They influence appearance and even cause functional disturbance, and place tremendous physiological and psychological burdens on patients. Therefore, pathological scars have been a challenge in plastic surgery and the focus of research.Blood supply is believed to be an important aspect in the development of pathological scars, and has thus attracted more attentions in recent years. However, there are controversies about blood supply in pathological scars.Hereby we summarized the advances of research on the blood supply in pathological scars, and explored future research directions. The vascular structure of pathological scars has different manifestations between hypertrophic scars and keloids. In terms of spatial vascular structure, blood vessels within hypertrophic scar tissues have a structure perpendicular to the skin surface, whereas those within keloid tissues present a typical dispersed, extended vascular structure. VASCULARITY OF PATHOLOGICAL SCARS 5,6The diameter or patency of the blood vessels of pathological scar remains controversial. Thaís et al used stereological methods to obtain information on pathological scar tissues with a microscope, and proposed that the blood vessels within the pathological scars were dilated compared with those in normal skin and normal scars.

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Hyperactivity of fibroblasts and functional regression of endothelial cells contribute to microvessel occlusion in hypertrophic scarring

Cited by 38 publications

References 44 publications

Hypertrophic scar regression is linked to the occurrence of endothelial dysfunction

Hypertrophic scar regression is linked to the occurrence of endothelial dysfunction

Wound Repair and Regeneration

The Characteristics of Blood Supply and Tissue Hypoxia in Pathological Scars

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