Topical axitinib suppresses angiogenesis pathways induced by pulsed dye laser

Abstract

Summary Background The recurrence of port-wine stain (PWS) blood vessels by pulsed dye laser (PDL)-induced angiogenesis is a critical barrier that must be overcome to achieve a better therapeutic outcome. Objectives To determine whether PDL-induced angiogenesis can be suppressed by topical axitinib. Methods The mRNA expression profiles of 86 angiogenic genes and phosphorylation levels of extracellular signal regulated kinases (ERKs), phosphorylated protein kinase B (AKT) and ribosomal protein S6 kinase (p70S6K) in rodent skin were examined with or without topical axitinib administration after PDL exposure. Results The PDL-induced increased transcriptional levels of angiogenic genes peaked at days 3–7 post-PDL exposure. Topical application of 0.5% axitinib effectively suppressed the PDL-induced increase in mRNA levels of the examined angiogenic genes and activation of AKT, P70S6K and ERK from days 1 to 7 post-PDL exposure. After topical administration, axitinib penetrated into rodent skin to an approximate depth of 929.5 μm. Conclusions Topical application of 0.5% axitinib can systematically suppress the PDL-induced early stages of angiogenesis via inhibition of the AKT/mammalian target of rapamycin/p70S6K and Src homology 2 domain containing transforming protein-1/mitogen-activated protein kinase kinase/ERK pathway cascades.

Characterization of Laser‐Resistant Port Wine Stain Blood Vessels Using In Vivo Reflectance Confocal Microscopy

“…Scale bar = 100 µm. stages of angiogenesis was ineffective [34,35]. These results may explain why rapamycin improves PWS lesion blanching in a limited subpopulation (~10%) of patients [36,37].…”

“…As a result, more angiogenic genes are transcribed and translated, leading to reformation, and reperfusion of blood vessels. We attempted to block this pathway using angiogenic inhibitors, such as rapamycin and axitinib , post‐PDL treatment. In rodent skin, both topical rapamycin and axitinib showed effective inhibition of the early stages of angiogenesis induced by PDL, but blockage of the late stages of angiogenesis was ineffective .…”

“…We attempted to block this pathway using angiogenic inhibitors, such as rapamycin and axitinib , post‐PDL treatment. In rodent skin, both topical rapamycin and axitinib showed effective inhibition of the early stages of angiogenesis induced by PDL, but blockage of the late stages of angiogenesis was ineffective . These results may explain why rapamycin improves PWS lesion blanching in a limited subpopulation (~10%) of patients .…”

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

“…Dear Editor , Port‐wine stain (PWS) is a congenital vascular malformation of human skin involving the superficial vascular plexus, but the molecular pathogenesis of these lesions is not completely understood . Herein, we performed a transmission electron microscopy (TEM) study to determine the main pathological characteristics and ultrastructure of various cell types, including endothelial cells (ECs), pericytes, fibroblasts and keratinocytes, in hypertrophic and nodular PWS.…”

A novel approach to port-wine stains

“…Indeed the risk of thrombotic events is high if the antiaggregant medication is stopped in the first year after percutaneous coronary intervention. 8 Finally the authors recommend minimizing the haemorrhagic risk by meticulous surgical techniques and elaborate haemostasis, pressure dressings and close postoperative follow-up. In our experience, in the case of wide excision or wide undermining, draining is recommended.…”