Ultrastructural characterization of hyperactive endothelial cells, pericytes and fibroblasts in hypertrophic and nodular port-wine stain lesions

Gao, Lin; Yin, Rong; Wang, H.; Guo, Weinan; Song, Wenting; Nelson, J. Stuart; Tan, Wenbin; Wang, G.

doi:10.1111/bjd.15373

Cited by 10 publications

(11 citation statements)

References 9 publications

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“…Another study of the main pathological features and ultrastructure of cell types in hypertrophic and nodular PWS, through the TEM, has shown that the main features were the presence of hyperactive ECs, pericytes, and fibroblasts. This has a major role in the proliferation and replication of the stroma, which may lead to the hypertrophic and nodular types of PWS [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Photodynamic Therapy Using HMME for Port-Wine Stains: Clinical Effectiveness and Sonographic Appearance

Khalaf

Sun

Wang

et al. 2020

BioMed Research International

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This study aims at exploring the clinical efficacy and sonographic changes of photodynamic therapy (PDT) using Hematoporphyrin Monomethyl Ether (HMME) for the treatment of port-wine stains (PWS). Forty-five patients with PWS were recruited between March 2017 and June 2018 from the Department of Dermatology of The Third Affiliated Hospital of Soochow University. Five cases were of the pink type, thirty-nine cases were of the purple-red type, and one case was of the thickened type. All patients received three treatment sessions of PDT. After covering normal skin outside the treated area, patients received an intravenous injection of 5 mg/kg HMME within 20 minutes. The affected areas were exposed to a 532 nm LED light and were kept vertically at a distance of 10 cm. The irradiation energy density was set between 80 and 110 J/cm2 in 15-minute sessions. Intermittent power density adjustment was performed at a rate of 5 mW/cm2, and the treatment was withheld when the endpoint reaction appeared. Three follow-ups were performed before and after treatment, respectively, and the efficacy, thickness, and density of skin before and after treatment were evaluated with high-frequency ultrasound. The overall efficacy rate was 97.78% in forty-five cases after treatment for three sessions. Efficacy was related to age (P=0.029) and lesion severity (P<0.001). There were significant differences in the efficacy between the groups of <18 years old, 18-29 years old, and >29 years old (P=0.029). A marked decrease in the numbers of distorted enlarged blood vessels per unit of the lesion was observed under high-frequency ultrasound. There were significant differences in skin thickness and skin density before and after treatment (F=14.528, 5.428, P<0.001). The swelling was reported to varying degrees in the treated areas in 23 patients with cheek lesion and in 6 frontal lesions. Hyperpigmentation after inflammation was observed in four patients that faded spontaneously after two months. In conclusion, photodynamic therapy for the treatment of PWS using HMME is effective and safe with few adverse reactions. Moreover, monitoring the changes in skin thickness and density of lesion tissue using high-frequency ultrasound can objectively evaluate the clinical efficacy of HMME photodynamic therapy and provide the basis for the formulation of individualized photodynamic therapy.

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Section: Introductionmentioning

confidence: 99%

Photodynamic Therapy Using HMME for Port-Wine Stains: Clinical Effectiveness and Sonographic Appearance

Khalaf

Sun

Wang

et al. 2020

BioMed Research International

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“…During the past decade, evidence has systematically documented the pathological characteristics of PWS/SWS, including detailed transmission electron microscopy (TEM) ultrastructure from infantile, hypertrophic and nodular PWS, molecular profiles and upregulation of exocytosis of PWS ECs [1,37,38,39]. These recent data have demonstrated that PWS is a multifactorial malformation, involving not only the vasculature, but also other structures within the dermis.…”

Section: Pathological Phenotypes Of Pws/swsmentioning

confidence: 99%

Section: Pathological Phenotypes Of Pws/swsmentioning

confidence: 99%

“…In hypertrophic and nodular PWS, hyperactive and proliferative ECs, pericytes and fibroblasts are observed [37]. These cells contain large numbers of rough endoplasmic reticulum, stacks of Golgi complexes, vesicles, free ribosomes and distended mitochondria in the cytoplasm [37]. These predominant ultrastructural characteristics represent a highly biosynthetic and metabolic state of these cells [37] and are the typical characteristics of endothelial progenitor cells (EPCs) [40,41].…”

Section: Pathological Phenotypes Of Pws/swsmentioning

confidence: 99%

“…These cells contain large numbers of rough endoplasmic reticulum, stacks of Golgi complexes, vesicles, free ribosomes and distended mitochondria in the cytoplasm [37]. These predominant ultrastructural characteristics represent a highly biosynthetic and metabolic state of these cells [37] and are the typical characteristics of endothelial progenitor cells (EPCs) [40,41]. More recently, we have identified hundreds of differentially expressed (DE) proteins in PWS lesions as compared to normal skin using a proteomics approach.…”

Section: Pathological Phenotypes Of Pws/swsmentioning

confidence: 99%

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The Pathogenesis of Port Wine Stain and Sturge Weber Syndrome: Complex Interactions between Genetic Alterations and Aberrant MAPK and PI3K Activation

Nguyen

Hochman

Mihm

et al. 2019

IJMS

100

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Port wine stain (PWS) is a congenital vascular malformation involving human skin. Approximately 15–20% of children a facial PWS involving the ophthalmic (V1) trigeminal dermatome are at risk for Sturge Weber syndrome (SWS), a neurocutaneous disorder with vascular malformations in the cerebral cortex on the same side of the facial PWS lesions. Recently, evidence has surfaced that advanced our understanding of the pathogenesis of PWS/SWS, including discoveries of somatic genetic mutations (GNAQ, PI3K), MAPK and PI3K aberrant activations, and molecular phenotypes of PWS endothelial cells. In this review, we summarize current knowledge on the etiology and pathology of PWS/SWS based on evidence that the activation of MAPK and/or PI3K contributes to the malformations, as well as potential futuristic treatment approaches targeting these aberrantly dysregulated signaling pathways. Current data support that: (1) PWS is a multifactorial malformation involving the entire physiological structure of human skin; (2) PWS should be pathoanatomically re-defined as “a malformation resulting from differentiation-impaired endothelial cells with a progressive dilatation of immature venule-like vasculatures”; (3) dysregulation of vascular MAPK and/or PI3K signaling during human embryonic development plays a part in the pathogenesis and progression of PWS/SWS; and (4) sporadic low frequency somatic mutations, such as GNAQ, PI3K, work as team players but not as a lone wolf, contributing to the development of vascular phenotypes. We also address many crucial questions yet to be answered in the future research investigations.

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Current clinical evidence is insufficient to support HMME–PDT as the first choice of treatment for young children with port wine birthmarks

Gao,

Nguyen,

Hochman

et al. 2024

Lasers Surg Med

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BackgroundPort wine birthmark (PWB) is a congenital vascular malformation of the skin. Pulsed dye laser (PDL) is the “gold standard” for the treatment of PWB globally. Hematoporphyrin monomethyl ether (HMME or hemoporfin)‐mediated photodynamic therapy (HMME–PDT) has emerged as the first choice for PWB treatment, particularly for young children, in many major hospitals in China during the past several decades.AimTo evaluate whether HMME–PDT is superior to PDL by comparing the clinical efficacies of both modalities.MethodPubMed records were searched for all relevant studies of PWB treatment using PDL (1988−2023) or HMME–PDT (2007−2023). Patient characteristics and clinical efficacies were extracted. Studies with a quartile percentage clearance or similar scale were included. A mean color clearance index (CI) per study was calculated and compared among groups. An overall CI (C0), with data weighted by cohort size, was used to evaluate the final efficacy for each modality.ResultA total of 18 HMME–PDT studies with 3910 patients in China were eligible for inclusion in this analysis. Similarly, 40 PDL studies with 5094 patients from nine different countries were eligible for inclusion in this analysis. Over 58% of patients in the HMME‐PDT studies were minors (<18 years old). A significant portion (21.3%) were young children (<3 years old). Similarly, 33.2% of patients in the PDL studies were minors. A small proportion (9.3%) was young children. The overall clearance rates for PDL were slightly, but not significantly, higher than those for HMME–PDT in cohorts with patients of all ages (C0, 0.54 vs. 0.48, p = 0.733), subpopulations with only minors (C0, 0.54 vs. 0.46, p = 0.714), and young children (C0, 0.67 vs. 0.50, p = 0.081). Regrettably, there was a lack of long‐term data on follow‐up evaluations for efficacy and impact of HMME‐PDT on young children in general, and central nervous system development in particular, because their blood‐brain barriers have a greater permeability as compared to adults.ConclusionPDL shows overall albeit insignificantly higher clearance rates than HMME‐PDT in patients of all ages; particularly statistical significance is nearly achieved in young children. Collectively, current evidence is insufficient to support HMME–PDT as the first choice of treatment of PWBs in young children given: (1) overall inferior efficacy as compared to PDL; (2) risk of off‐target exposure to meningeal vasculature during the procedure; (3) administration of steriods for mitigation of side effects; ‐and (4) lack of long‐term data on the potential impact of HMME on central nervous system development in young children.

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Ultrastructural characterization of hyperactive endothelial cells, pericytes and fibroblasts in hypertrophic and nodular port-wine stain lesions

Cited by 10 publications

References 9 publications

Photodynamic Therapy Using HMME for Port-Wine Stains: Clinical Effectiveness and Sonographic Appearance

Photodynamic Therapy Using HMME for Port-Wine Stains: Clinical Effectiveness and Sonographic Appearance

The Pathogenesis of Port Wine Stain and Sturge Weber Syndrome: Complex Interactions between Genetic Alterations and Aberrant MAPK and PI3K Activation

Current clinical evidence is insufficient to support HMME–PDT as the first choice of treatment for young children with port wine birthmarks

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