title: Expression of transforming growth factor beta 1-related signaling proteins in irradiated vessels.
abstract: OBJECTIVE
  Microvascular free tissue transfer is a standard method in head and neck reconstructive surgery. However, previous radiotherapy of the operative region is associated with an increased incidence in postoperative flap-related complications and complete flap loss. As transforming growth factor beta (TGF-β) 1 and galectin-3 are well known markers in the context of fibrosis and lectin-like oxidized low-density lipoprotein 1 (LOX-1) supports vascular atherosclerosis, the aim of this study was to evaluate the expression of TGF-β1 and related markers as well as LOX-1 in irradiated vessels.
  
  
  METHODS
  To evaluate the expression of galectin-3, Smad 2/3, TGF-β1, and LOX-1, 20 irradiated and 20 nonirradiated arterial vessels were used for immunohistochemical staining. We semiquantitatively assessed the ratio of stained cells/total number of cells (labeling index).
  
  
  RESULTS
  Expression of galectin-3, Smad 2/3, and TGF-β1 was significantly increased in previously irradiated vessels compared with nonirradiated controls. Furthermore, LOX-1 was expressed significantly higher in irradiated compared with nonirradiated vessels.
  
  
  CONCLUSIONS
  Fibrosis-related proteins like galectin-3, Smad 2/3, and TGF-β1 are upregulated after radiotherapy and support histopathological changes leading to vasculopathy of the irradiated vessels. Furthermore, postoperative complications in irradiated patients can be explained by increased endothelial dysfunction caused by LOX-1 in previously irradiated patients. Consequently, not only TGF-β1 but also galectin-3 inhibitors may decrease complications after microsurgical tissue transfer.
authors.affiliation: Department of Oral and Maxillofacial Surgery, University of Erlangen- Nürnberg, Glückstraße 11, 91054, Erlangen, Germany, raimund.preidl@uk-erlangen.de.
authors.forename: Raimund H M
authors.initials: RH
authors.lastname: Preidl
authors.forename: Patrick
authors.initials: P
authors.lastname: Möbius
authors.forename: Manuel
authors.initials: M
authors.lastname: Weber
authors.forename: Kerstin
authors.initials: K
authors.lastname: Amann
authors.forename: Friedrich W
authors.initials: FW
authors.lastname: Neukam
authors.forename: Andreas
authors.initials: A
authors.lastname: Schlegel
authors.forename: Falk
authors.initials: F
authors.lastname: Wehrhan
mesh_terms: D001158:Arteries / Q000378:metabolism* / Q000528:radiation effects*; D016207:Cytokines / Q000378:metabolism*; D004307:Dose-Response Relationship, Radiation; D037502:Galectin 3 / Q000378:metabolism*; D006801:Humans; D011829:Radiation Dosage; D051127:Scavenger Receptors, Class E / Q000378:metabolism*; D015398:Signal Transduction / Q000528:radiation effects; D014018:Tissue Distribution; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D016207:Cytokines; D037502:Galectin 3; C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E; D053773:Transforming Growth Factor beta1