FGF23 protein expression in coronary arteries is associated with impaired kidney function - PubMed (original) (raw)

FGF23 protein expression in coronary arteries is associated with impaired kidney function

Natalie A van Venrooij et al. Nephrol Dial Transplant. 2014 Aug.

Abstract

Background: Fibroblast growth factor 23 (FGF23) levels are elevated in chronic kidney disease (CKD) and elevated values have been associated with both heart disease and mortality. Recent studies show that FGF23, a protein synthesized by osteocytes, is also present in calcified atherosclerotic plaques and may be induced by heart disease. Whether vascular expression of FGF23 is associated with progressive CKD, however, remains unknown. Therefore, the relationship between kidney function, vascular calcification and FGF23 expression was evaluated in patients with heart disease.

Methods: Immunohistochemistry for FGF23 was performed in coronary arteries of all patients undergoing heart transplantation at UCLA between February 2008 and 2010. Immunohistochemical staining for Klotho, DMP1, FGFR1, and FGFR3; calcium deposition; and RNA expression of Klotho and DMP1 were assessed in a subset of eight samples.

Results: FGF23 was detected by immunohistochemistry in 56% of the coronary artery specimens. Vascular FGF23 expression correlated with declining kidney function, as evidenced by reduced creatinine clearance. FGFR1 and FGFR3 were detected throughout the vascular tissue and in calcified plaques. Calcium deposition, Klotho expression and DMP1 expression correlated with FGF23 immunoreactivity.

Conclusions: The findings suggest that the Klotho-FGF23-FGFR system is active in coronary arteries and its upregulation correlates with impaired renal function and matrix calcium deposition.

Keywords: arteriosclerosis; immunohistochemistry; kidney.

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Figures

FIGURE 1:

Immunohistochemical staining for (A) FGF23, (B) DMP1, (C) OPN and (D) Klotho and (E) calcium staining in sequential sections of calcified coronary artery (magnification: ×200). Red/brown staining (arrows) indicates immunoreactivity for each protein and/or calcium, respectively. FGF23, fibroblast growth factor 23; DMP1, dentin matrix protein 1; OPN, osteopontin.

FIGURE 2:

Immunohistochemical staining for (A) CD68 and (B) FGF23 in foamy macrophages. Red staining (arrows) indicates immunoreactivity. Immunofluorescence staining for (C) CD68 (green) and (D) FGF23 (red) and in calcified coronary artery. (E) Co-localization of the two proteins is demonstrated by the yellow color on merging of the two images. Blue color indicates DAPI staining. CD68, cluster of differentiation 68 (monocyte/macrophage lineage marker); FGF23, fibroblast growth factor 23.

FIGURE 3:

Immunoreactivity for fibroblast growth factor receptor 3 (FGFR3) and fibroblast growth factor receptor 1 (FGFR1) was present diffusely throughout the tunica intima and media as well as in calcified areas of coronary artery. (A) Immunohistochemical staining for FGFR3 and (B) immunohistochemical staining for FGFR1 in the tunica intima and media (×40 magnification). Red staining (arrows) indicates immunoreactivity. Arrowheads demarcate the border between the tunica intima and media. (C) Immunoreactivity for FGFR3 and (D) immunoreactivity for FGFR1 in calcified plaque (×200 magnification). Red staining (arrows) indicates immunoreactivity. Arrowheads demarcate the edge of the calcified lesion.

FIGURE 4:

Immunofluorescence staining for FGF23, DMP1 and Klotho in calcified coronary artery. (A) FGF23 (red) and (B) DMP1 (green) in coronary artery. (C) Yellow color on merging (A) and (B) indicates co-localization FGF23 and DMP1. (D) Immunofluorescence staining for FGF23 (red) and (E) Klotho (green) in coronary artery. (F) Yellow color on merging (D) and (E) indicates co-localization Klotho and FGF23. Blue color indicates DAPI staining. FGF23, fibroblast growth factor 23; DMP1, dentin matrix protein 1.

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FGF23 protein expression in coronary arteries is associated with impaired kidney function - PubMed (original) (raw)