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Int J Cardiol. 2013 Apr 30;165(1):179-83. doi: 10.1016/j.ijcard.2011.08.850. Epub 2011 Sep 25.

Expression of FGF23/KLOTHO system in human vascular tissue.

Author information

1
Research Unit, University Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.

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.

PMID:
21945708
DOI:
10.1016/j.ijcard.2011.08.850
[Indexed for MEDLINE]

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