Angiogenesis and proliferation of endothelial cells in hypertrophic and nodular port-wine stain

Background:Port-wine stain(PWS)has been classified not as the hyperplasia of cells,but rather,as an expansion of malformed vessels.However,previous studies have reported upregulated expression of proangiogenic factors in PWS.Several studies have indicated that the pathology exhibits proliferation of numerous endothelial cells in hypertrophic/nodular PWS.This study aimed to determine the expression of vascular epithelial growth factor(VEGF),matrix metalloproteinase-9(MMP-9),angiopoietin-2(ANG-2),and basic fibroblast growth factor(bFGF)in hypertrophic PWS.Methods:Immunohistochemistry was used to analyze skin samples from 33 patients with hypertrophic PWS.Expression levels of VEGF,MMP-9,ANG-2,and bFGF in hypertrophic PWS were determined by multiplying the intensity by the percentage of immunoreactive cells.Immunoreactivity scores were classified as follows:negative(0),low(1),moderate(2,3,and 4),or high(6).Results:Based on pathological characteristics,hypertrophic PWS was divided into vascular malformation and pyogenic granuloma(PG)types.VEGF,MMP-9,ANG-2,and bFGF were significantly activated in the blood vessels of PG-type PWS samples compared with their counterparts in blood vessels of vascular malformation-type PWS samples and controls.PG-type hypertrophic PWS,which exhibited proliferation of endothelial cells,showed the strongest activation.Conclusion:The exuberant proliferation of endothelial cells in PG-type hypertrophic PWS may be associated with the regulation of proangiogenic factors during development.These proangiogenic factors that function in the angiogenesis and proliferation of endothelial cells may play an important role in the pathogenesis and progression of PWS.Furthermore,these factors may be dynamic and behave differently in various types of hypertrophic PWS.

Sturge–Weber syndrome:an update for the pediatrician

Sturge–Weber syndrome(SWS)is a rare congenital neurocutaneous disorder characterized by the simultaneous presence of both cutaneous and extracutaneous capillary malformations.SWS usually presents as a facial port-wine birthmark,with a varying presence of leptomeningeal capillary malformations and ocular vascular abnormalities.The latter may lead to significant neurological and ocular morbidity such as epilepsy and glaucoma.SWS is most often caused by a somatic mutation involving the G protein subunit alpha Q or G protein subunit alpha 11 gene causing various alterations in downstream signaling pathways.We specifically conducted a comprehensive review focusing on the current knowledge of clinical practices,the latest pathophysiological insights,and the potential novel therapeutic avenues they provide.Data sources A narrative,non-systematic review of the literature was conducted,combining expert opinion with a balanced review of the available literature.A search of PubMed,Google Scholar and Embase was conducted,using keywords“Sturge–Weber Syndrome”OR“SWS”,“Capillary malformations”,“G protein subunit alpha 11”OR“G protein subunit alpha Q”.Results One of the hallmark features of SWS is the presence of a port-wine birthmark at birth,and forehead involvement is most indicative for SWS.The most common ocular manifestations of SWS are glaucoma and choroidal hemangioma.Glaucoma presents in either in infancy(0–3 years of age)or later in life.Neurological complications are common in SWS,occurring in about 70%–80%of patients,with seizures being the most common one.SWS significantly impacts the quality of life for patients and their families,and requires a multidisciplinary approach for diagnosis and treatment.Currently,no disease-modifying therapies exist,and treatment is mostly focused on symptoms or complications as they arise.Conclusions SWS remains a complex and heterogeneous disorder.Further research is needed to optimize diagnostic and therapeutic strategies,and to translate insights from molecular pathogenesis to clinical practice.