title: Topical rapamycin systematically suppresses the early stages of pulsed dye laser-induced angiogenesis pathways.
abstract: BACKGROUND
  Administration of topical rapamycin (RPM) suppresses the regeneration and revascularization of photocoagulated blood vessels induced by pulsed dye laser (PDL).
  
  
  OBJECTIVE
  To systematically elucidate the molecular pathophysiology of the inhibition of PDL-induced angiogenesis by topical RPM in a rodent model.
  
  
  METHODS
  The mRNA expression profiles of 86 angiogenic genes and phosphorylation levels of ribosomal protein S6 kinase (P70S6K) in rodent skin were examined with or without topical RPM administration post-PDL exposure.
  
  
  RESULTS
  The PDL-induced systematic increases in transcriptional levels of angiogenic genes showed a peak expression at days 3-7 post-PDL in rodent skin. Topical application of 1% RPM significantly and systematically suppressed the PDL-induced increase in mRNA levels of the examined angiogenic genes during the first five days post-PDL. The phosphorylation levels of P70S6K increased after PDL exposure but those increases were suppressed by the topical RPM. After topical application, RPM penetrated to an approximate depth of 768.4 μm into rodent skin.
  
  
  CONCLUSIONS
  Topical application of 1% RPM can significantly and systematically suppress the PDL-induced early stage of angiogenesis via inhibition of the AKT/mTOR/P70S6K pathway in a rodent model.
authors.affiliation: Department of Surgery and Biomedical Engineering, Beckman Laser Institute and Medical Clinic, University of California, Irvine, 92612, California; Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Gao
authors.forename: Sydney
authors.initials: S
authors.lastname: Phan
authors.forename: Dawnica Mercado
authors.initials: DM
authors.lastname: Nadora
authors.forename: Margarita
authors.initials: M
authors.lastname: Chernova
authors.forename: Victor
authors.initials: V
authors.lastname: Sun
authors.forename: Salena Marie Oaxaca
authors.initials: SM
authors.lastname: Preciado
authors.forename: Brittany
authors.initials: B
authors.lastname: Ballew
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Jia
authors.forename: Wangcun
authors.initials: W
authors.lastname: Jia
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Martin C
authors.initials: MC
authors.lastname: Mihm
authors.forename: J Stuart
authors.initials: JS
authors.lastname: Nelson
authors.forename: Wenbin
authors.initials: W
authors.lastname: Tan
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D054025:Lasers, Dye; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020123:Sirolimus / Q000008:administration & dosage*; D012867:Skin / Q000098:blood supply* / Q000187:drug effects* / Q000528:radiation effects
chemical_list: D007166:Immunosuppressive Agents; D036341:Intercellular Signaling Peptides and Proteins; D020123:Sirolimus
keywords: P70S6K; Pulsed dye laser; angiogenesis; port wine stain; rapamycin