title: Expression of FGF23/KLOTHO system in human vascular tissue.
abstract: BACKGROUND
  Fibroblast growth factor (FGF)-23 levels have been associated with impaired vasoreactivity, increased arterial stiffness, and cardiovascular morbi-mortality, whereas a protective function of KLOTHO against endothelial dysfunction has been reported. Since expression of the FGF23-KLOTHO system in human vascular tissue remains unproved, we aimed to study the expression of FGF23, FGF receptors (FGFR) and KLOTHO in human aorta. In addition, we analyzed the FGF23-KLOTHO expression in occlusive coronary thrombi.
  
  
  METHODS
  Thoracic aorta specimens from 44 patients underwent elective cardiac surgery, and thrombus material from 2 patients with acute coronary syndrome (ACS), were tested for FGF23-KLOTHO system expression.
  
  
  RESULTS
  Expression of KLOTHO (mean expression level 4.85 ± 5.43, arbitrary units) and two of the three cognate FGFR (FGFR-1 and -3) were detected and confirmed by RT-PCR, sequencing and qRT-PCR. KLOTHO expression was confirmed within occlusive coronary thrombi from patients with ACS. However, expression of FGF23 and FGFR4 was not observed. We also detected the aortic expression of membrane-anchored A Desintegrin and Metalloproteinases (ADAM)-17, the enzyme responsible for the shedding of KLOTHO from the cell surface, and the anti-inflammatory cytokine interleukin (IL)-10. Interestingly, in aortic samples there was a direct association between KLOTHO mRNA levels and those of ADAM-17 and IL-10 (r = 0.54, P<0.001; r = 0.51, P<0.01, respectively).
  
  
  CONCLUSIONS
  Human vascular tissue expresses members of the FGF23-KLOTHO system, indicating that it can be a direct target organ for FGF23. In addition, KLOTHO expression is also detected in occlusive coronary thrombi. These findings suggest a putative role of FGF23-KLOTHO axis in human vascular pathophysiology and cardiovascular disease.
authors.affiliation: Research Unit, University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Donate-Correa
authors.forename: Carmen
authors.initials: C
authors.lastname: Mora-Fernández
authors.forename: Rafael
authors.initials: R
authors.lastname: Martínez-Sanz
authors.forename: Mercedes
authors.initials: M
authors.lastname: Muros-de-Fuentes
authors.forename: Horacio
authors.initials: H
authors.lastname: Pérez
authors.forename: Beatriz
authors.initials: B
authors.lastname: Meneses-Pérez
authors.forename: Violeta
authors.initials: V
authors.lastname: Cazaña-Pérez
authors.forename: Juan F
authors.initials: JF
authors.lastname: Navarro-González
mesh_terms: D054058:Acute Coronary Syndrome / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D001013:Aorta, Thoracic / Q000378:metabolism* / Q000473:pathology; D003328:Coronary Thrombosis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D005966:Glucuronidase / Q000096:biosynthesis*; D006801:Humans; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged
chemical_list: C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins