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Fibroblast growth factor 23 is not associated with and does not induce arterial calcification.

Scialla JJ, Lau WL, Reilly MP, Isakova T, Yang HY, Crouthamel MH, Chavkin NW, Rahman M, Wahl P, Amaral AP, Hamano T, Master SR, Nessel L, Chai B, Xie D, Kallem RR, Chen J, Lash JP, Kusek JW, Budoff MJ, Giachelli CM, Wolf M, Chronic Renal Insufficiency Cohort Study Investigato - Kidney Int. (2013)

Bottom Line: Neither FGF23 nor serum phosphate were consistently associated with thoracic aorta calcium.Whereas elevated phosphate concentrations induced calcification in vitro, FGF23 had no effect on phosphate uptake or phosphate-induced calcification regardless of phosphate concentration or even in the presence of soluble klotho.Thus, in contrast to serum phosphate, FGF23 is not associated with arterial calcification and does not promote calcification experimentally.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.

ABSTRACT
Elevated fibroblast growth factor 23 (FGF23) is associated with cardiovascular disease in patients with chronic kidney disease. As a potential mediating mechanism, FGF23 induces left ventricular hypertrophy; however, its role in arterial calcification is less clear. In order to study this, we quantified coronary artery and thoracic aorta calcium by computed tomography in 1501 patients from the Chronic Renal Insufficiency Cohort (CRIC) study within a median of 376 days (interquartile range 331-420 days) of baseline. Baseline plasma FGF23 was not associated with the prevalence or severity of coronary artery calcium after multivariable adjustment. In contrast, higher serum phosphate levels were associated with prevalence and severity of coronary artery calcium, even after adjustment for FGF23. Neither FGF23 nor serum phosphate were consistently associated with thoracic aorta calcium. We could not detect mRNA expression of FGF23 or its coreceptor, klotho, in human or mouse vascular smooth muscle cells, or normal or calcified mouse aorta. Whereas elevated phosphate concentrations induced calcification in vitro, FGF23 had no effect on phosphate uptake or phosphate-induced calcification regardless of phosphate concentration or even in the presence of soluble klotho. Thus, in contrast to serum phosphate, FGF23 is not associated with arterial calcification and does not promote calcification experimentally. Hence, phosphate and FGF23 promote cardiovascular disease through distinct mechanisms.

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(A) RT-PCR did not detect fibroblast growth factor 23 (FGF23) or klotho cDNA in human vascular smooth muscle cells (VSMCs), using primer sets that have previously been described.32 FGF23 positive control from plasmid cDNA (expected band size 649 bp), and klotho positive control from human kidney cDNA (expected band size 349 bp).(B) In cultured human VSMCs, FGF23 did not induce calcification under control conditions (1.4 mM phosphate) and did not augment calcification under high-phosphate conditions (2.6 mM phosphate). Data are mean ± s.d. and p-values for the two phosphate conditions are shown.(C) FGF23 with or without soluble klotho did not affect phosphate-induced calcification of mouse aortic rings (n = 5 per group). Data are mean ± s.d. and p-value for the high-phosphate groups is shown.
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Figure 3: (A) RT-PCR did not detect fibroblast growth factor 23 (FGF23) or klotho cDNA in human vascular smooth muscle cells (VSMCs), using primer sets that have previously been described.32 FGF23 positive control from plasmid cDNA (expected band size 649 bp), and klotho positive control from human kidney cDNA (expected band size 349 bp).(B) In cultured human VSMCs, FGF23 did not induce calcification under control conditions (1.4 mM phosphate) and did not augment calcification under high-phosphate conditions (2.6 mM phosphate). Data are mean ± s.d. and p-values for the two phosphate conditions are shown.(C) FGF23 with or without soluble klotho did not affect phosphate-induced calcification of mouse aortic rings (n = 5 per group). Data are mean ± s.d. and p-value for the high-phosphate groups is shown.

Mentions: Consistent with a recent report,32 we detected expression of FGF receptors (FGFR)1 and FGFR3 in cultured human vascular smooth muscle cells (VSMCs) by reverse transcription PCR (RT-PCR, data not shown). In contrast, we did not detect expression of FGF23 or its co-receptor, klotho in human or mouse cultured VSMCs by RT-PCR (Figure 3a). To investigate whether expression might be induced in CKD, we analyzed aortas from mice after partial renal ablation and dietary phosphate loading to promote uremic vascular calcification.33 FGF23 and klotho were not detected in any pooled sample of mouse aorta (2–3 aortas per pool) from 12 CKD mice, 6 of which had calcification as indicated by aortic arch calcium content and aortic expression of the osteochondrogenic markers,33 or from 7 healthy controls (data not shown).


Fibroblast growth factor 23 is not associated with and does not induce arterial calcification.

Scialla JJ, Lau WL, Reilly MP, Isakova T, Yang HY, Crouthamel MH, Chavkin NW, Rahman M, Wahl P, Amaral AP, Hamano T, Master SR, Nessel L, Chai B, Xie D, Kallem RR, Chen J, Lash JP, Kusek JW, Budoff MJ, Giachelli CM, Wolf M, Chronic Renal Insufficiency Cohort Study Investigato - Kidney Int. (2013)

(A) RT-PCR did not detect fibroblast growth factor 23 (FGF23) or klotho cDNA in human vascular smooth muscle cells (VSMCs), using primer sets that have previously been described.32 FGF23 positive control from plasmid cDNA (expected band size 649 bp), and klotho positive control from human kidney cDNA (expected band size 349 bp).(B) In cultured human VSMCs, FGF23 did not induce calcification under control conditions (1.4 mM phosphate) and did not augment calcification under high-phosphate conditions (2.6 mM phosphate). Data are mean ± s.d. and p-values for the two phosphate conditions are shown.(C) FGF23 with or without soluble klotho did not affect phosphate-induced calcification of mouse aortic rings (n = 5 per group). Data are mean ± s.d. and p-value for the high-phosphate groups is shown.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3672330&req=5

Figure 3: (A) RT-PCR did not detect fibroblast growth factor 23 (FGF23) or klotho cDNA in human vascular smooth muscle cells (VSMCs), using primer sets that have previously been described.32 FGF23 positive control from plasmid cDNA (expected band size 649 bp), and klotho positive control from human kidney cDNA (expected band size 349 bp).(B) In cultured human VSMCs, FGF23 did not induce calcification under control conditions (1.4 mM phosphate) and did not augment calcification under high-phosphate conditions (2.6 mM phosphate). Data are mean ± s.d. and p-values for the two phosphate conditions are shown.(C) FGF23 with or without soluble klotho did not affect phosphate-induced calcification of mouse aortic rings (n = 5 per group). Data are mean ± s.d. and p-value for the high-phosphate groups is shown.
Mentions: Consistent with a recent report,32 we detected expression of FGF receptors (FGFR)1 and FGFR3 in cultured human vascular smooth muscle cells (VSMCs) by reverse transcription PCR (RT-PCR, data not shown). In contrast, we did not detect expression of FGF23 or its co-receptor, klotho in human or mouse cultured VSMCs by RT-PCR (Figure 3a). To investigate whether expression might be induced in CKD, we analyzed aortas from mice after partial renal ablation and dietary phosphate loading to promote uremic vascular calcification.33 FGF23 and klotho were not detected in any pooled sample of mouse aorta (2–3 aortas per pool) from 12 CKD mice, 6 of which had calcification as indicated by aortic arch calcium content and aortic expression of the osteochondrogenic markers,33 or from 7 healthy controls (data not shown).

Bottom Line: Neither FGF23 nor serum phosphate were consistently associated with thoracic aorta calcium.Whereas elevated phosphate concentrations induced calcification in vitro, FGF23 had no effect on phosphate uptake or phosphate-induced calcification regardless of phosphate concentration or even in the presence of soluble klotho.Thus, in contrast to serum phosphate, FGF23 is not associated with arterial calcification and does not promote calcification experimentally.

View Article: PubMed Central - PubMed

Affiliation: Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.

ABSTRACT
Elevated fibroblast growth factor 23 (FGF23) is associated with cardiovascular disease in patients with chronic kidney disease. As a potential mediating mechanism, FGF23 induces left ventricular hypertrophy; however, its role in arterial calcification is less clear. In order to study this, we quantified coronary artery and thoracic aorta calcium by computed tomography in 1501 patients from the Chronic Renal Insufficiency Cohort (CRIC) study within a median of 376 days (interquartile range 331-420 days) of baseline. Baseline plasma FGF23 was not associated with the prevalence or severity of coronary artery calcium after multivariable adjustment. In contrast, higher serum phosphate levels were associated with prevalence and severity of coronary artery calcium, even after adjustment for FGF23. Neither FGF23 nor serum phosphate were consistently associated with thoracic aorta calcium. We could not detect mRNA expression of FGF23 or its coreceptor, klotho, in human or mouse vascular smooth muscle cells, or normal or calcified mouse aorta. Whereas elevated phosphate concentrations induced calcification in vitro, FGF23 had no effect on phosphate uptake or phosphate-induced calcification regardless of phosphate concentration or even in the presence of soluble klotho. Thus, in contrast to serum phosphate, FGF23 is not associated with arterial calcification and does not promote calcification experimentally. Hence, phosphate and FGF23 promote cardiovascular disease through distinct mechanisms.

Show MeSH
Related in: MedlinePlus