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Membrane trafficking and exocytosis are upregulated in port wine stain blood vessels.

ABSTRACT: INTRODUCTION:Port wine stain (PWS) is characterized as a progressive dilatation of immature venule-like vasculatures which result from differentiation-impaired endothelial cells. In this study, we aimed to identify the major biological pathways accounting for the pathogenesis of PWS. METHODS:Sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS) was used to identify differentially expressed proteins in PWS lesions, followed by confirmative studies with immunohistochemistry, immunoblot and transmission electron microscopy (TEM). RESULTS:107 out of 299 identified proteins showed differential expressions in PWS lesions as compared to normal skin, mainly involving the functions of biosynthesis, membrane trafficking, cytoskeleton and cell adhesion/migration. The confirmative studies showed that expressions of membrane trafficking/exocytosis related proteins such as VAT1, IQGAP1, HSC70, clathrin, perlecan, spectrin ?1 and GDIR1 were significantly increased in PWS blood vessels as compared to normal ones; while collagen subtypes 6A1 and 6A3 were decreased in PWS skin. Furthermore, TEM studies showed there is a significant upregulation of extracellular vesicle exocytosis from PWS blood vessels as compared to control. CONCLUSIONS:The biological process of membrane trafficking and exocytosis is enhanced in PWS blood vessels. Our results imply that the extracellular vesicles released by lesional endothelial cells may act as potential intercellular signaling mediators to contribute to the pathogenesis of PWS.

SUBMITTER: Yin R

PROVIDER: S-EPMC6594380 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Membrane trafficking and exocytosis are upregulated in port wine stain blood vessels.

Yin Rong R Rice Shawn J SJ Wang Jinwei J Gao Lin L Tsai Joseph J Anvari Radean T RT Zhou Fang F Liu Xin X Wang Gang G Tang Yuxin Y Mihm Martin C MC Belani Chandra P CP Chen Dong-Bao DB Nelson J Stuart JS Tan Wenbin W

Histology and histopathology 20181010 5

<h4>Introduction</h4>Port wine stain (PWS) is characterized as a progressive dilatation of immature venule-like vasculatures which result from differentiation-impaired endothelial cells. In this study, we aimed to identify the major biological pathways accounting for the pathogenesis of PWS.<h4>Methods</h4>Sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS) was used to identify differentially expressed proteins in PWS lesions, followed by confirmative studies ...[more]

PMID: 30302745

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Project description:Background and objectivesPhotodynamic therapy (PDT) has shown potentially beneficial results in treating port-wine stain, but its benefit-risk profile remains undefined. This study aimed to evaluate the efficacy and safety of PDT conducted with hemoporfin and a 532 nm continuous wave laser to treat port-wine stain clinically.Patients and methodsThis randomized clinical trial was conducted in eight hospitals in China. Participants were adolescent and adult patients (age range: 14-65 years old) with port-wine stain. During stage 1 (day 1 to week 8) all patients were randomized at a 3:1 ratio to treatment (532 nm laser irradiation (96-120 J/cm2) with hemoporfin (5mg/kg; PDT-hemoporfin, n = 330)) or placebo groups (irradiation with placebo (PDT-placebo, n = 110)); during stage 2 (week 8 to 16) patients in both groups were offered treatment. Clinician-evaluators, who were blind to the study, classified each case on the following four-level scale according to assessment of before and after standardized pictures of the lesion area: no improvement: <20%; some improvement: 20-59%; great improvement: 60-89%; or nearly completely resolved: ≥90%. The primary efficacy endpoint was proportion of patients achieving at least some improvement at week 8. The secondary efficacy endpoints were proportion of patients achieving nearly completely resolved or at least great improvement at week 8, proportion of patients achieving early completely resolved, at least great improvement, or at least some improvement at week 16, and the corresponding satisfaction of the investigators and the patients (designated as 'excellent', 'good', 'moderate', or 'ineffective') at weeks 8 and 16.ResultsCompared to the PDT-placebo group, the PDT-hemoporfin group showed a significantly higher proportion of patients that achieved at least some improvement (89.7% [n = 295; 95% CI, 85.9%-92.5%] vs. 24.5% [n = 27; 95% CI, 17.4%-33.3%]) at week 8 (P < 0.0001) and higher improvements for all secondary efficacy endpoints. Treatment reactions occurred in 99.5% (n = 731; 95% CI, 98.7%-99.8%) of the PDT-hemoporfin treatments (n = 735). Hyperpigmentation occurred in 22.9 per 100 patient-treatments (n = 168; 95% CI, 20.0-26.0) in the PDT-hemoporfin treated patients.ConclusionsHemoporfin-mediated PDT is an effective and safe treatment option for adolescent and adult patients with port-wine stain.Trial registrationChinese Clinical Trial Registry ChiCTR-TRC-08000213.

Project description:Background: Port-wine stain (PWS) is a congenital capillary malformation occurring commonly in the head and neck. Left untreated, affected areas may darken and hypertrophy over time, resulting in pronounced disfigurement, risk of spontaneous hemorrhage, and functional impairment. The burden of hypertrophic facial PWS and the benefit of laser therapy have not heretofore been well characterized. Herein, the health utility of these two states is assessed among naïve observers. Methods: Naïve observers (n = 262) ranked the utility of four randomized health states (monocular blindness, binocular blindness, hypertrophic facial PWS, and laser-treated facial PWS) by means of visual analogue scale (VAS), standard gamble (SG), and time trade-off (TTO) techniques. Health states are presented using standardized facial photographs. Results: Health utilities (VAS, SG, and TTO) were reported as follows (mean ± standard deviation): monocular blindness (0.73 ± 0.21, 0.86 ± 0.21, 0.87 ± 0.18), binocular blindness (0.51 ± 0.26, 0.72 ± 0.27, 0.69 ± 0.27), hypertrophic facial PWS (0.71 ± 0.24, 0.83 ± 0.23, 0.83 ± 0.21), and laser-treated facial PWS (0.87 ± 0.16, 0.91 ± 0.18, 0.92 ± 0.16). Laser-treated facial PWS showed significantly higher utility measures than the untreated hypertrophic state (p < 0.001, all measures), with a difference of 3.24 quality-adjusted life years. Linear regression analysis revealed that non-Caucasian race and higher level of education were associated with lower SG and TTO utility scores for the hypertrophic facial PWS state among naïve observers. Conclusions: Societal-perceived utility of hypertrophic facial PWS is similar to that of monocular blindness. Laser-treated facial PWS is perceived significantly more favorably than the untreated hypertrophic state. These findings provide insight into the societal burden of facial PWS and impact of laser treatment, facilitating objective comparisons with other disparate disease states.

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Membrane trafficking and exocytosis are upregulated in port wine stain blood vessels.

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Membrane trafficking and exocytosis are upregulated in port wine stain blood vessels.

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