title: Effect of aging and cardiovascular risk factors on receptor Tie1 expression in human erectile tissue.
abstract: BACKGROUND
  Erectile dysfunction is highly prevalent in patients with advanced age or cardiovascular disease risk factors (CVDRFs). These conditions interfere on expression of vascular growth factors and respective receptors causing disturbance in endothelial function.
  
  
  OBJECTIVE
  This study aims to assess the effect of aging and CVDRF on the expression of tyrosine kinase with immunoglobulin-like and EGF-like domains (Tie) 1 in human corpus cavernosum (CC).
  
  
  METHODS
  CC fragments obtained from programmed surgeries or organ donors were divided into three groups: young, healthy aged, and aged with CVDRF. Angiopoietin (Ang) 1, Ang2, Tie1, and Tie2 mRNA and protein levels were assessed by real-time polymerase chain reaction and Western blotting, respectively. Dual-immunolabeling of Tie1 with specific markers of endothelium and smooth muscle and Ang1 and Ang2 was performed.
  
  
  METHODS
  To characterize the expression of Tie1 in human CC and elucidate its potential inhibitory effect in Ang-Tie2 system.
  
  
  RESULTS
  Analysis of mRNAs demonstrated a decrease in Tie1 expression in CVDRF individuals compared with aged or young healthy individuals. No variation for Tie2, Ang1, or Ang2 expression was observed among the studied groups. In all analyzed CC fragments, a 125 kDa band, Tie1, was detected. This protein presented a significant age-related decrease, specially in individuals with CVDRF. Immunofluorescence study revealed Tie1 expression in the endothelium of samples of all experimental groups.
  
  
  CONCLUSIONS
  Employing different methodological approaches, we show for the first time that Tie1 is expressed in human CC endothelium, and its level of expression diminishes in aged individuals, particularly those with CVDRF. This finding reinforces the view that delivery of Ang1 to the CC of erectile dysfunction affected CVDRF patients is able to activate a beneficial Tie2 response.
authors.affiliation: Department of Experimental Biology, Faculty of Medicine, Universidade do Porto, Porto, Portugal; Institute for Molecular and Cell Biology (IBMC), Universidade do Porto, Porto, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Fonseca
authors.forename: Nuno
authors.initials: N
authors.lastname: Tomada
authors.forename: Alexandre
authors.initials: A
authors.lastname: Magalhães
authors.forename: Adriana R
authors.initials: AR
authors.lastname: Rodrigues
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Gouveia
authors.forename: Delminda
authors.initials: D
authors.lastname: Neves
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000378:metabolism*; D042683:Angiopoietin-1 / Q000096:biosynthesis; D042702:Angiopoietin-2 / Q000096:biosynthesis; D015153:Blotting, Western; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D004727:Endothelium / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D010413:Penis / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D042810:Receptor, TIE-1 / Q000096:biosynthesis*; D042787:Receptor, TIE-2 / Q000096:biosynthesis; D012307:Risk Factors
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D012333:RNA, Messenger; D042810:Receptor, TIE-1; D042787:Receptor, TIE-2
keywords: Aging; Angiopoietins; Cardiovascular Disease Risk Factors; Erectile Dysfunction; Human Corpus Cavernosum; Tie1