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To date, the mechanisms underlying the pathogenesis and progression of PWSs are yet to be clearly elucidated. The potential reasons for dilated vessels are as follows: (1) somatic GNAQ (R183Q) mutations that form enlarged capillary malformation-like vessels through angiopoietin-2, (2) decreased perivascular nerve elements, (3) the coexistence of Eph receptor B1 and ephrin B2, and (4) the deficiency of \u03b1SMA expression in pericytes. In addition, ERK, c-JNK, P70S6K, AKT, PI3K, and PKC are assumed to be involved in PWS development. Although pulsed-dye laser (PDL) remains the gold standard for treating PWSs, the recurrence rate is high. Topical drugs, including imiquimod, axitinib, and rapamycin, combined with PDL treatments, are expected to alter the recurrence rate and reduce the number of PDL sessions for PWSs. For the deep vascular plexus, photosensitizers or photothermal transduction agents encapsulated by nanocarriers conjugated to surface markers (CD133\/CD166\/VEGFR-2) possess a promising therapeutic potential in photodynamic therapy or photothermal therapy for PWSs. The pathogenesis, progression, and treatment of PWSs should be extensively investigated.<\/jats:p>","DOI":"10.3390\/ijms232012139","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T05:31:18Z","timestamp":1665552678000},"page":"12139","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Pathogenesis of Port-Wine Stains: Directions for Future Therapies"],"prefix":"10.3390","volume":"23","author":[{"given":"Lian","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Dermatology, West China Hospital, Sichuan University, Chengdu 610017, China"},{"name":"Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology (CIII), Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Dermatology, West China Hospital, Sichuan University, Chengdu 610017, China"},{"name":"Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology (CIII), Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Dermatology, West China Hospital, Sichuan University, Chengdu 610017, China"},{"name":"Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology (CIII), Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610017, China"},{"name":"Department of Medical Cosmetology, Chengdu Second People\u2019s Hospital, Chengdu 610056, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, West China Hospital, Sichuan University, Chengdu 610017, China"},{"name":"Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology (CIII), Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5109-6055","authenticated-orcid":false,"given":"Xian","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Dermatology, West China Hospital, Sichuan University, Chengdu 610017, China"},{"name":"Laboratory of Dermatology, Clinical Institute of Inflammation and Immunology (CIII), Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610017, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1111\/j.1525-1470.1983.tb01093.x","article-title":"The incidence and significance of birthmarks in a cohort of 4641 newborns","volume":"1","author":"Alper","year":"1983","journal-title":"Pediatr Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s10103-009-0726-8","article-title":"Spectrophotometers for the clinical assessment of port-wine stain skin lesions: A review","volume":"25","author":"Lister","year":"2010","journal-title":"Lasers Med Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"110901","DOI":"10.1117\/1.JBO.17.11.110901","article-title":"Simulating light transport through skin for color prediction of port wine stain lesions: A review","volume":"17","author":"Lister","year":"2012","journal-title":"J. Biomed. Opt."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/j.1524-4725.1991.tb01597.x","article-title":"The medical necessity of evaluation and treatment of port-wine stains","volume":"17","author":"Geronemus","year":"1991","journal-title":"J. Dermatol. Surg. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1097\/DSS.0000000000000525","article-title":"The natural history of soft tissue hypertrophy, bony hypertrophy, and nodule formation in patients with untreated head and neck capillary malformations","volume":"41","author":"Lee","year":"2015","journal-title":"Dermatol. Surg."},{"key":"ref_6","first-page":"48","article-title":"Facial port-wine stains and Sturge-Weber syndrome","volume":"76","author":"Enjolras","year":"1985","journal-title":"Pediatrics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1542\/peds.87.3.323","article-title":"Location of port-wine stains and the likelihood of ophthalmic and\/or central nervous system complications","volume":"87","author":"Tallman","year":"1991","journal-title":"Pediatrics"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1097\/00000637-198806000-00002","article-title":"Port-wine stain\u2014A surgical and psychological problem","volume":"20","author":"Malm","year":"1988","journal-title":"Ann. Plast. Surg."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1111\/j.1365-2133.1989.tb01800.x","article-title":"Psychological disabilities amongst patients with port wine stains","volume":"121","author":"Lanigan","year":"1989","journal-title":"Br. J. Dermatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1111\/jdv.15599","article-title":"Port wine stain treatment outcomes have not improved over the past three decades","volume":"33","author":"Chohan","year":"2019","journal-title":"J. Eur. Acad. Dermatol. Venereol. JEADV"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1111\/1346-8138.15238","article-title":"Retrospective study of photodynamic therapy for pulsed dye laser-resistant port-wine stains","volume":"47","author":"Han","year":"2020","journal-title":"J. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1111\/bjd.12204","article-title":"Pulsed dye laser-resistant port-wine stains: Mechanisms of resistance and implications for treatment","volume":"168","author":"Savas","year":"2013","journal-title":"Br. J. Dermatol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Faurschou, A., Olesen, A.B., Leonardi-Bee, J., and Haedersdal, M. (2011). Lasers or light sources for treating port-wine stains. Cochrane Database Syst. Rev., CD007152.","DOI":"10.1002\/14651858.CD007152.pub2"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1111\/bjd.12130","article-title":"Side-by-side comparison of photodynamic therapy and pulsed-dye laser treatment of port-wine stain birthmarks","volume":"168","author":"Gao","year":"2013","journal-title":"Br. J. Dermatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1080\/14764170701817023","article-title":"Comparison study of a long-pulse pulsed dye laser and a long-pulse pulsed alexandrite laser in the treatment of port wine stains","volume":"10","author":"Li","year":"2008","journal-title":"J. Cosmet. Laser Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.pdpdt.2007.12.001","article-title":"Comparison of photodynamic therapy and pulsed dye laser in patients with port wine stain birthmarks: A retrospective analysis","volume":"5","author":"Yuan","year":"2008","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Tu, P., Zhou, G., Zhou, Z., Lin, X., Yang, H., Lu, Z., Gao, T., Tu, Y., and Xie, H. (2016). Hemoporfin photodynamic therapy for port-wine stain: A randomized controlled trial. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0156219"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1111\/jdv.12021","article-title":"Long-pulsed 1064 nm Nd:YAG laser improves hypertrophic port-wine stains","volume":"27","author":"Bosveld","year":"2013","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e13925","DOI":"10.1111\/dth.13925","article-title":"Successful treatment of hypertrophic and nodular port-wine stains with intralesional 1064 nm Nd: YAG laser","volume":"33","author":"Liu","year":"2020","journal-title":"Dermatol. Ther."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1002\/lsm.20793","article-title":"Treatment of hypertrophic and resistant port wine stains with a 755 nm laser: A case series of 20 patients","volume":"41","author":"Izikson","year":"2009","journal-title":"Lasers Surg. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1159\/000248712","article-title":"Immunohistological evaluation of endothelial markers and basement membrane components in port-wine stains","volume":"176","author":"Mitsuhashi","year":"1988","journal-title":"Dermatologica"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1001\/archderm.1994.01690070073011","article-title":"Immunohistochemistry of port-wine stains and normal skin with endothelium-specific antibodies PAL-E, anti-ICAM-1, anti-ELAM-1, and anti-factor VIIIrAg","volume":"130","author":"Neumann","year":"1994","journal-title":"Arch. Dermatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1001\/archderm.1984.01650470059013","article-title":"Port-wine stains. Morphologic variations and developmental lesions","volume":"120","author":"Finley","year":"1984","journal-title":"Arch. Dermatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1097\/DAD.0b013e3181e169f5","article-title":"Nodules arising within port-wine stains: A clinicopathologic study of 31 cases","volume":"33","author":"Chen","year":"2011","journal-title":"Am. J. Dermatopathol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Liu, L., Zhou, L., Zhao, Q., Li, X., Yang, L., Li, E., Wei, D., and Jiang, X. (2022). Histological analysis of different types of port-wine stains to guide clinical decision making: A retrospective study. Indian J. Dermatol. Venereol. Leprol., 1\u20139.","DOI":"10.25259\/IJDVL_730_2021"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1001\/archderm.1982.01650240015012","article-title":"Immunofluorescent staining with antibodies to factor VIII, fibronectin, and collagenous basement membrane protein in normal human skin and port wine stains","volume":"118","author":"Finley","year":"1982","journal-title":"Arch. Dermatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1111\/bjd.15716","article-title":"Coexistence of Eph receptor B1 and ephrin B2 in port-wine stain endothelial progenitor cells contributes to clinicopathological vasculature dilatation","volume":"177","author":"Tan","year":"2017","journal-title":"Br. J. Dermatol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nature13165","article-title":"Capillary pericytes regulate cerebral blood flow in health and disease","volume":"508","author":"Hall","year":"2014","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1038\/nature05193","article-title":"Bidirectional control of CNS capillary diameter by pericytes","volume":"443","author":"Peppiatt","year":"2006","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00401-018-1893-0","article-title":"Targeting pericytes for therapeutic approaches to neurological disorders","volume":"136","author":"Cheng","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1111\/bjd.15068","article-title":"Pathological alterations involve the entire skin physiological milieu in infantile and early childhood port wine stain","volume":"177","author":"Tan","year":"2016","journal-title":"Br. J. Dermatol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1007\/BF00426611","article-title":"Ultrastructural observations in port wine stains","volume":"280","author":"Schneider","year":"1988","journal-title":"Arch. Dermatol. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e2003065","DOI":"10.1002\/adma.202003065","article-title":"Metal-organic-framework-engineered enzyme-mimetic catalysts","volume":"32","author":"Ma","year":"2020","journal-title":"Adv. Mater."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1111\/j.1399-0004.2012.01926.x","article-title":"Monozygotic twins discordant for port wine stains support the post-zygotic mutation hypothesis","volume":"83","author":"Chen","year":"2013","journal-title":"Clin. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1111\/j.1365-2230.1997.tb01053.x","article-title":"Demographic study of port wine stain patients attending a laser clinic: Family history, prevalence of naevus anaemicus and results of prior treatment","volume":"22","author":"Mills","year":"1997","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"204","DOI":"10.3109\/14764172.2015.1007060","article-title":"Heredity of port-wine stains: Investigation of families without a RASA1 mutation","volume":"17","author":"Lauritzen","year":"2015","journal-title":"J. Cosmet. Laser Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"E12","DOI":"10.1136\/jmg.37.8.e12","article-title":"A family with hereditary port wine stain","volume":"37","author":"Berg","year":"2000","journal-title":"J. Med. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/sj.ejhg.5200817","article-title":"Locus for susceptibility for familial capillary malformation (\u2018port-wine stain\u2019) maps to 5q","volume":"10","author":"Eerola","year":"2002","journal-title":"Eur. J. Hum. Genet. EJHG"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1056\/NEJMoa1213507","article-title":"Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ","volume":"368","author":"Shirley","year":"2013","journal-title":"New Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.jaad.2015.09.063","article-title":"The somatic GNAQ mutation (R183Q) is primarily located within the blood vessels of port wine stains","volume":"74","author":"Tan","year":"2016","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"77e","DOI":"10.1097\/PRS.0000000000001868","article-title":"Endothelial cells from capillary malformations are enriched for somatic GNAQ mutations","volume":"137","author":"Couto","year":"2016","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1111\/bjd.16830","article-title":"Somatic GNAQ mutation in different structures of port-wine macrocheilia","volume":"179","author":"Ma","year":"2018","journal-title":"Br. J. Dermatol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4143","DOI":"10.1002\/hed.25962","article-title":"Phenotypic association of presence of a somatic GNAQ mutation with port-wine stain distribution in capillary malformation","volume":"41","author":"Lee","year":"2019","journal-title":"Head Neck"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e75","DOI":"10.1111\/ijd.14335","article-title":"Novel GNAQ mutation(R183G) of Port-wine stains: First case in East Asia","volume":"58","author":"Cai","year":"2019","journal-title":"Int. J. Dermatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e105","DOI":"10.1111\/bjd.15373","article-title":"Ultrastructural characterization of hyperactive endothelial cells, pericytes and fibroblasts in hypertrophic and nodular port wine stain lesions","volume":"177","author":"Gao","year":"2017","journal-title":"Br. J. Dermatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.ccell.2019.01.009","article-title":"A Platform of synthetic lethal gene interaction networks reveals that the GNAQ uveal melanoma oncogene controls the hippo pathway through FAK","volume":"35","author":"Feng","year":"2019","journal-title":"Cancer Cell"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"10156","DOI":"10.1038\/ncomms10156","article-title":"The experimental power of FR900359 to study Gq-regulated biological processes","volume":"6","author":"Schrage","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.sbi.2017.05.004","article-title":"Understanding the GPCR biased signaling through G protein and arrestin complex structures","volume":"45","author":"Zhou","year":"2017","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41594-017-0011-7","article-title":"Structure and dynamics of GPCR signaling complexes","volume":"25","author":"Hilger","year":"2018","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.sbi.2021.03.013","article-title":"The conformational transition during G protein-coupled receptor (GPCR) and G protein interaction","volume":"69","author":"Ahn","year":"2021","journal-title":"Curr. Opin. Struct. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1126\/science.1071550","article-title":"G protein pathways","volume":"296","author":"Neves","year":"2002","journal-title":"Science"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e27","DOI":"10.1161\/ATVBAHA.121.316651","article-title":"Endothelial GNAQ p.R183Q increases ANGPT2 (Angiopoietin-2) and drives formation of enlarged blood vessels","volume":"42","author":"Huang","year":"2022","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1001\/jamadermatol.2014.1244","article-title":"Novel genetic mutations in a sporadic port-wine stain","volume":"150","author":"Lian","year":"2014","journal-title":"JAMA Dermatol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1002\/ajmg.a.61403","article-title":"Growth hormone deficiency in megalencephaly-capillary malformation syndrome: An association with activating mutations in PIK3CA","volume":"182","author":"Davis","year":"2020","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1016\/j.ajhg.2012.05.006","article-title":"Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome","volume":"90","author":"Kurek","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1084\/jem.20181353","article-title":"Somatic activating mutations in PIK3CA cause generalized lymphatic anomaly","volume":"216","author":"Agra","year":"2019","journal-title":"J. Exp. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1128\/MCB.06222-11","article-title":"The chromatin-remodeling enzymes BRG1 and CHD4 antagonistically regulate vascular Wnt signaling","volume":"32","author":"Curtis","year":"2012","journal-title":"Mol. Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1242\/dev.087379","article-title":"BRG1 promotes COUP-TFII expression and venous specification during embryonic vascular development","volume":"140","author":"Davis","year":"2013","journal-title":"Development"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4597","DOI":"10.1111\/bph.12718","article-title":"EPH receptor\/ephrin system: In the quest for novel anti-angiogenic therapies: Commentary on Hassan-Mohamed et al., Br. J. Pharmacol. 171: 5195\u20135208","volume":"172","author":"Hatziapostolou","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1016\/j.jaad.2014.07.025","article-title":"Sustained activation of c-Jun N-terminal and extracellular signal-regulated kinases in port-wine stain blood vessels","volume":"71","author":"Tan","year":"2014","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1097\/DAD.0000000000000785","article-title":"Activation of PKCalpha and PI3K kinases in hypertrophic and nodular port wine stain lesions","volume":"39","author":"Yin","year":"2017","journal-title":"Am. J. Dermatopathol."},{"key":"ref_62","first-page":"479","article-title":"Membrane trafficking and exocytosis are upregulated in port wine stain blood vessels","volume":"34","author":"Yin","year":"2019","journal-title":"Histol. Histopathol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s11910-012-0323-2","article-title":"Uses of skin biopsy for sensory and autonomic nerve assessment","volume":"13","author":"Myers","year":"2013","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1097\/00006534-199103000-00003","article-title":"Ectatic blood vessels in port-wine stains lack innervation: Possible role in pathogenesis","volume":"87","author":"Rydh","year":"1991","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_65","first-page":"892","article-title":"Confocal microscopy study of nerves and blood vessels in untreated and treated port wine stains: Preliminary observations","volume":"30","author":"Selim","year":"2004","journal-title":"Dermatol. Surg."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1111\/j.1365-2133.1990.tb07283.x","article-title":"Reduced vasoactive responses in port wine stains","volume":"122","author":"Lanigan","year":"1990","journal-title":"Br. J. Dermatol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/0306-9877(87)90031-4","article-title":"Pathogenesis of port wine stains. A new hypothesis","volume":"22","author":"Rosen","year":"1987","journal-title":"Med. Hypotheses"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1111\/j.1365-4362.1993.tb01478.x","article-title":"Cosmetic tattooing as a treatment of port-wine stains","volume":"32","author":"Stolz","year":"1993","journal-title":"Int. J. Dermatol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/0007-1226(79)90090-0","article-title":"The treatment of port wine stains by cryosurgery: A preliminary report","volume":"32","author":"Sharpe","year":"1979","journal-title":"Br. J. Plast. Surg."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1111\/j.1524-4725.1982.tb01091.x","article-title":"CO2 laser treatment of port-wine stains: A preliminary report","volume":"8","author":"Ratz","year":"1982","journal-title":"J. Dermatol. Surg. Oncol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1126\/science.6836297","article-title":"Selective photothermolysis: Precise microsurgery by selective absorption of pulsed radiation","volume":"220","author":"Anderson","year":"1983","journal-title":"Science"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1046\/j.1365-2133.1998.02351.x","article-title":"Port-wine stains unresponsive to pulsed dye laser: Explanations and solutions","volume":"139","author":"Lanigan","year":"1998","journal-title":"Br. J. Dermatol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1001\/archotol.1996.01890230022005","article-title":"Port-wine stains. An assessment of 5 years of treatment","volume":"122","author":"Orten","year":"1996","journal-title":"Arch. Otolaryngol. Head Neck Surg."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1046\/j.1365-2133.2000.03893.x","article-title":"Recurrence of port-wine stains after treatment with the flashlamp-pumped pulsed dye laser","volume":"143","author":"Michel","year":"2000","journal-title":"Br. J. Dermatol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1111\/1523-1747.ep12365566","article-title":"Photothermally induced vessel-wall necrosis after pulsed dye laser treatment: Lack of response in port-wine stains with small sized or deeply located vessels","volume":"107","author":"Fiskerstrand","year":"1996","journal-title":"J. Investig. Dermatol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1007\/s10103-021-03478-9","article-title":"Wavelength optimization for the laser treatment of port wine stains","volume":"37","author":"Li","year":"2022","journal-title":"Lasers Med. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1080\/14764170802524452","article-title":"Treatment endpoints for resistant port wine stains with a 755 nm laser","volume":"11","author":"Izikson","year":"2009","journal-title":"J. Cosmet. Laser Ther."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1007\/s11684-018-0623-2","article-title":"Classification and treatment of orbital venous malformations: An updated review","volume":"13","author":"Li","year":"2019","journal-title":"Front. Med."},{"key":"ref_79","first-page":"699","article-title":"Port-wine stain nodules in the adult: Report of 20 cases treated by CO2 laser vaporization","volume":"27","author":"Fonseca","year":"2001","journal-title":"Dermatol. Surg."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1002\/lsm.23083","article-title":"Predictive value of dermoscopy for the treatment of port-wine stains with large spot 532 nm laser","volume":"51","author":"Kwiek","year":"2019","journal-title":"Lasers Surg. Med."},{"key":"ref_81","first-page":"572","article-title":"Usefulness of three-dimensional digital image analysis for objective evaluation of the efficacy of non-facial port-wine stain treatment with large spot 532 nm laser","volume":"37","author":"Kwiek","year":"2020","journal-title":"Postepy Derm. Alergol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1097\/DSS.0000000000003114","article-title":"Combination therapy of pulsed dye laser with intense pulsed light in port-wine stain treatment: A prospective side-by-side comparison","volume":"47","author":"Yu","year":"2021","journal-title":"Dermatol. Surg."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1111\/j.1365-2133.2008.08993.x","article-title":"Pulsed dye laser vs. intense pulsed light for port-wine stains: A randomized side-by-side trial with blinded response evaluation","volume":"160","author":"Faurschou","year":"2009","journal-title":"Br. J. Dermatol."},{"key":"ref_84","first-page":"7","article-title":"Intense pulsed light source for the treatment of dye laser resistant port-wine stains","volume":"5","author":"Bjerring","year":"2003","journal-title":"J. Cosmet. Laser Ther."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/lsm.22087","article-title":"Microarray analysis of port wine stains before and after pulsed dye laser treatment","volume":"45","author":"Laquer","year":"2013","journal-title":"Lasers Surg. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1111\/bjd.13439","article-title":"Topical axitinib suppresses angiogenesis pathways induced by pulsed dye laser","volume":"172","author":"Gao","year":"2015","journal-title":"Br. J. Dermatol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.otohns.2008.07.015","article-title":"The expression of vascular endothelial growth factor and its receptors in port-wine stains","volume":"139","author":"Vural","year":"2008","journal-title":"Otolaryngol. Head Neck Surg. Off. J. Am. Acad. Otolaryngol. Head Neck Surg."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1517\/17460441.2015.1045411","article-title":"Axitinib: From preclinical development to future clinical perspectives in renal cell carcinoma","volume":"10","author":"Zakharia","year":"2015","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_89","first-page":"1185","article-title":"Infantile hemangioma: Pathogenesis and mechanisms of action of propranolol","volume":"15","author":"Rotter","year":"2017","journal-title":"J. Dtsch Dermatol. Ges."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1111\/bjd.12772","article-title":"Treatment of port wine stains with pulsed dye laser and topical timolol: A multicenter randomized controlled trial","volume":"170","author":"Passeron","year":"2014","journal-title":"Br. J. Dermatol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1111\/jdv.13275","article-title":"Treatment of resistant port-wine stains with bosentan and pulsed dye laser: A pilot prospective study","volume":"30","author":"Taquin","year":"2016","journal-title":"J. Eur. Acad. Dermatol. Venereol. JEADV"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1111\/j.0007-0963.2004.05898.x","article-title":"In vivo and in situ modulation of the expression of genes involved in metastasis and angiogenesis in a patient treated with topical imiquimod for melanoma skin metastases","volume":"150","author":"Hesling","year":"2004","journal-title":"Br. J. Dermatology."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1002\/lsm.20716","article-title":"Pilot study examining the combined use of pulsed dye laser and topical Imiquimod versus laser alone for treatment of port wine stain birthmarks","volume":"40","author":"Chang","year":"2008","journal-title":"Lasers Surg. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.jaad.2011.11.958","article-title":"Enhanced port-wine stain lightening achieved with combined treatment of selective photothermolysis and imiquimod","volume":"66","author":"Tremaine","year":"2012","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/j.1600-0560.2010.01520.x","article-title":"Stem cell marker upregulation in normal cutaneous vessels following pulsed-dye laser exposure and its abrogation by concurrent rapamycin administration: Implications for treatment of port-wine stain birthmarks","volume":"37","author":"Loewe","year":"2010","journal-title":"J. Cutan. Pathol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1002\/lsm.22101","article-title":"Topical rapamycin suppresses the angiogenesis pathways induced by pulsed dye laser: Molecular mechanisms of inhibition of regeneration and revascularization of photocoagulated cutaneous blood vessels","volume":"44","author":"Tan","year":"2012","journal-title":"Lasers Surg. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1002\/lsm.21141","article-title":"Observations on enhanced port wine stain blanching induced by combined pulsed dye laser and rapamycin administration","volume":"43","author":"Nelson","year":"2011","journal-title":"Lasers Surg. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1002\/lsm.22436","article-title":"Port wine stain treated with a combination of pulsed dye laser and topical rapamycin ointment","volume":"48","author":"Griffin","year":"2016","journal-title":"Lasers Surg. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jaad.2014.10.011","article-title":"Topical rapamycin combined with pulsed dye laser in the treatment of capillary vascular malformations in Sturge-Weber syndrome: Phase II, randomized, double-blind, intraindividual placebo-controlled clinical trial","volume":"72","author":"Marques","year":"2015","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"376","DOI":"10.5144\/0256-4947.2018.376","article-title":"Outcome with topical sirolimus for port wine stain malformations after unsatisfactory results with pulse dye laser treatment alone","volume":"38","author":"Musalem","year":"2018","journal-title":"Ann. Saudi. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1002\/lsm.22548","article-title":"Treatment of port wine stains using Pulsed Dye Laser, Erbium YAG Laser, and topical rapamycin (sirolimus)-A randomized controlled trial","volume":"49","author":"Greveling","year":"2017","journal-title":"Lasers Surg. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1111\/jocd.13867","article-title":"Evaluating the efficacy and safety of topical sirolimus 0.2% cream as adjuvant therapy with pulsed dye laser for the treatment of port wine stain: A randomized, double-blind, placebo-controlled trial","volume":"20","author":"Fallahi","year":"2021","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1080\/09546634.2017.1306018","article-title":"Prospective pilot study on combined use of pulsed dye laser and 1% topical rapamycin for treatment of nonfacial cutaneous capillary malformation","volume":"28","author":"Doh","year":"2017","journal-title":"J. Dermatol. Treat."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e13172","DOI":"10.1111\/dth.13172","article-title":"Treatment of port wine stain with Tixel-induced rapamycin delivery following pulsed dye laser application","volume":"33","author":"Artzi","year":"2020","journal-title":"Dermatol. Ther."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1007\/s13555-022-00699-w","article-title":"The efficacy of hematoporphyrin monomethyl ether photodynamic therapy in adult patients with port-wine stains: A retrospective study","volume":"12","author":"Zhang","year":"2022","journal-title":"Dermatol. Ther."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.pdpdt.2014.06.004","article-title":"Comparison of pulsed dye laser (PDL) and photodynamic therapy (PDT) for treatment of facial port-wine stain (PWS) birthmarks in pediatric patients","volume":"11","author":"Zhang","year":"2014","journal-title":"Photodiagnosis Photodyn. Ther."},{"key":"ref_107","first-page":"159","article-title":"Histological characteristics of port-wine stains with complete regression after photodynamic therapy treatment: A 7-year follow-up","volume":"40","author":"Han","year":"2022","journal-title":"Photobiomodul. Photomed. Laser Surg."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"50901","DOI":"10.1117\/1.JBO.21.5.050901","article-title":"Review on near-infrared heptamethine cyanine dyes as theranostic agents for tumor imaging, targeting, and photodynamic therapy","volume":"21","author":"Shi","year":"2016","journal-title":"J. Biomed. Opt."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Fernandez, M., and Orozco, J. (2021). Advances in functionalized photosensitive polymeric nanocarriers. Polymers, 13.","DOI":"10.3390\/polym13152464"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.2217\/nnm-2017-0130","article-title":"PLGA nanoparticles with CD133 aptamers for targeted delivery and sustained release of propranolol to hemangioma","volume":"12","author":"Guo","year":"2017","journal-title":"Nanomedicine"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1039\/C8CS00618K","article-title":"Photothermal therapy and photoacoustic imaging via nanotheranostics in fighting cancer","volume":"48","author":"Liu","year":"2019","journal-title":"Chem. Soc. Rev."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1038\/s41571-020-0410-2","article-title":"Clinical development and potential of photothermal and photodynamic therapies for cancer","volume":"17","author":"Li","year":"2020","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1007\/s10103-017-2158-1","article-title":"Nd:YAG laser-induced morphology change and photothermal conversion of gold nanorods with potential application in the treatment of port-wine stain","volume":"32","author":"Xing","year":"2017","journal-title":"Lasers Med. Sci."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1117\/1.JBO.23.12.121616","article-title":"Photothermal treatment of port-wine stains using erythrocyte-derived particles doped with indocyanine green: A theoretical study","volume":"23","author":"Burns","year":"2018","journal-title":"J. Biomed. Opt."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/20\/12139\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:50:21Z","timestamp":1760143821000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/20\/12139"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,12]]},"references-count":114,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms232012139"],"URL":"https:\/\/doi.org\/10.3390\/ijms232012139","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,12]]}}}