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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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Fibroblast growth factor 23 (50 ng/mL) with or without klotho (50 ng/mL) had no significant effect on sodium-dependent phosphate uptake in both mouse and human VSMCs. Data expressed as mean ± s.d. and p-values for the human and mouse data sets are presented.
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Figure 4: Fibroblast growth factor 23 (50 ng/mL) with or without klotho (50 ng/mL) had no significant effect on sodium-dependent phosphate uptake in both mouse and human VSMCs. Data expressed as mean ± s.d. and p-values for the human and mouse data sets are presented.

Mentions: FGF23 regulates expression of type II sodium-dependent phosphate cotransporters in the kidney,36 but its effect on the type III sodium-dependent phosphate cotransporters, PiT-1 and PiT-2, that mediate phosphate transport in VSMCs is unknown. We tested whether FGF23 regulates phosphate transport in VSMC by examining radiolabeled phosphate uptake in the presence of sodium chloride versus choline chloride to calculate sodium-dependent uptake. FGF23 (50 ng/mL) had no significant effect on phosphate uptake in the presence or absence of soluble klotho (50 ng/mL), in either mouse or human VSMCs (Figure 4).


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)

Fibroblast growth factor 23 (50 ng/mL) with or without klotho (50 ng/mL) had no significant effect on sodium-dependent phosphate uptake in both mouse and human VSMCs. Data expressed as mean ± s.d. and p-values for the human and mouse data sets are presented.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 4: Fibroblast growth factor 23 (50 ng/mL) with or without klotho (50 ng/mL) had no significant effect on sodium-dependent phosphate uptake in both mouse and human VSMCs. Data expressed as mean ± s.d. and p-values for the human and mouse data sets are presented.
Mentions: FGF23 regulates expression of type II sodium-dependent phosphate cotransporters in the kidney,36 but its effect on the type III sodium-dependent phosphate cotransporters, PiT-1 and PiT-2, that mediate phosphate transport in VSMCs is unknown. We tested whether FGF23 regulates phosphate transport in VSMC by examining radiolabeled phosphate uptake in the presence of sodium chloride versus choline chloride to calculate sodium-dependent uptake. FGF23 (50 ng/mL) had no significant effect on phosphate uptake in the presence or absence of soluble klotho (50 ng/mL), in either mouse or human VSMCs (Figure 4).

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