Expression of FGF23/KLOTHO system in human vascular tissue

Abstract

BackgroundFibroblast 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. MethodsThoracic 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. ResultsExpression 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). ConclusionsHuman 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.