title: Fibroblast growth factor 23 is not associated with and does not induce arterial calcification.
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.
authors: Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
authors: Julia J
authors: JJ
authors: Scialla
authors: Wei Ling
authors: WL
authors: Lau
authors: Muredach P
authors: MP
authors: Reilly
authors: Tamara
authors: T
authors: Isakova
authors: Hsueh-Ying
authors: HY
authors: Yang
authors: Matthew H
authors: MH
authors: Crouthamel
authors: Nicholas W
authors: NW
authors: Chavkin
authors: Mahboob
authors: M
authors: Rahman
authors: Patricia
authors: P
authors: Wahl
authors: Ansel P
authors: AP
authors: Amaral
authors: Takayuki
authors: T
authors: Hamano
authors: Stephen R
authors: SR
authors: Master
authors: Lisa
authors: L
authors: Nessel
authors: Boyang
authors: B
authors: Chai
authors: Dawei
authors: D
authors: Xie
authors: Radhakrishna R
authors: RR
authors: Kallem
authors: Jing
authors: J
authors: Chen
authors: James P
authors: JP
authors: Lash
authors: John W
authors: JW
authors: Kusek
authors: Matthew J
authors: MJ
authors: Budoff
authors: Cecilia M
authors: CM
authors: Giachelli
authors: Myles
authors: M
authors: Wolf
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001013:Aorta, Thoracic / Q000000981:diagnostic imaging / Q000378:metabolism*; D001018:Aortic Diseases / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology; D001027:Aortography / Q000379:methods; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D016009:Chi-Square Distribution; D017023:Coronary Angiography / Q000379:methods; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000378:metabolism*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood* / Q000235:genetics; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000090265:Klotho Proteins; D016015:Logistic Models; D008297:Male; D051379:Mice; D008875:Middle Aged; D015999:Multivariate Analysis; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D010710:Phosphates / Q000097:blood; D015995:Prevalence; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D014481:United States / Q000453:epidemiology; D015854:Up-Regulation; D061205:Vascular Calcification / Q000097:blood* / Q000000981:diagnostic imaging / Q000453:epidemiology; D055815:Young Adult
chemical_list: C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D010710:Phosphates; D012333:RNA, Messenger; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins; D002118:Calcium
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