Expression of FGF23/KLOTHO system in human vascular tissue

Donate-Correa, Javier; Mora‐Fernández, Carmen; Martínez‐Sanz, Rafael; Muros‐de‐Fuentes, Mercedes; Perez, Horacio; Meneses-Pérez, Beatriz; Cazaña-Pérez, Violeta; Navarro‐González, Juan F.

doi:10.1016/j.ijcard.2011.08.850

Cited by 106 publications

(90 citation statements)

References 35 publications

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“…CKD is a state of klotho deficiency, which may contribute to accelerated vascular calcification (27). Members of the FGF system have also been found in pathology specimens of human aorta, although confirmatory studies are lacking (28). Some cross-sectional studies have found an association between FGF-23 and the presence or severity of CAC (9)(10)(11)29), but this is not a universal finding (12).…”

Section: Discussionmentioning

confidence: 99%

FGF-23 and the Progression of Coronary Arterial Calcification in Patients New to Dialysis

Khan

Chirinos

Litt³

et al. 2012

Clinical Journal of the American Society of Nephrology

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SummaryBackground and objective Fibroblast growth factor 23 (FGF-23), a regulator of phosphorus metabolism, is a risk marker in CKD. FGF-23 has been associated with coronary arterial calcification (CAC), but it is not known whether FGF-23 predicts CAC progression in CKD. The aim of this study was to evaluate the association of FGF-23 with CAC progression in advanced CKD.Design, setting, participants, & measurements FGF-23 levels and CAC were measured by electrocardiographytriggered multislice computed tomography in 99 individuals initiating dialysis. Patients were enrolled in the study from April 2008 to July 2010. CAC was calculated using Agatston and calcium volume score. Sixty-seven study participants had repeat CAC measures at 1 year. Linear regression was used to assess the association of FGF-23 with CAC.Results The mean age of study participants was 50 years; 33% were women, and 64% were black. The median FGF-23 level was 1238 relative units (RU)/ml (interquartile range, 515-2218 RU/ml). According to Agatston score, FGF-23 was not associated with baseline CAC (P=0.14) but was significantly associated with CAC progression. There was a 192.3-Agatston unit change in CAC score per 1-SD change in FGF-23 (P=0.008) in models adjusting for known risk factors for CAC and serum phosphate. This association persisted after adjustment for high-sensitivity C-reactive protein, 25-OH vitamin D levels, and the use of phosphorus binders. Results were similar when change in calcium volume score was used.Conclusions In individuals with advanced CKD, serum FGF-23 is strongly associated with CAC progression. FGF-23 may be a marker of cardiovascular risk in CKD.

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Section: Discussionmentioning

confidence: 99%

FGF-23 and the Progression of Coronary Arterial Calcification in Patients New to Dialysis

Khan

Chirinos

Litt³

et al. 2012

Clinical Journal of the American Society of Nephrology

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“…The recent demonstration of the expression of the FGF receptors and Klotho in the human vascular wall reinforce the possibility that they may influence vessel integrity (4,5 ). Interestingly, recent studies (5,30 ) point to the absence of Klotho protein and gene expression in mouse vascular tissue.…”

Section: Cardiovascular Disease and Mortalitymentioning

confidence: 95%

“…In addition, genetic studies have demonstrated that Klotho gene (KL) polymorphisms are associated with the incidence of coronary artery disease (32 ). The recently described expression of Klotho in human vascular smooth muscle cells may partially contribute to explain these effects over the cardiovascular system (4,5 ).…”

Section: Cardiovascular Disease and Mortalitymentioning

confidence: 99%

“…Prospective clinical studies have demonstrated an association between FGF-23 concentrations and cardiovascular risk factors and mortality. The expression of Klotho in vascular tissue (4,5 ), combined with the identification of its soluble form (3 ), has allowed consideration of whether this molecule exerts direct effects in multiple organs, including those of the cardiovascular system. Diverse commercial assays are currently available for determination of human FGF-23 and Klotho.…”

confidence: 99%

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Pathophysiological Implications of Fibroblast Growth Factor-23 and Klotho and Their Potential Role as Clinical Biomarkers

et al. 2014

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BACKGROUND Fibroblast growth factor-23 (FGF-23) and Klotho constitute the main regulatory system of phosphorus homeostasis. Beyond this physiological role, there is growing evidence suggesting that this system has relevant pathophysiological implications in different clinical processes. CONTENT In this review we discuss the pathophysiological implications of the FGF-23/Klotho system and the potential utility that measurements of its components may have as clinical biomarkers in different clinical settings, such as progression of chronic kidney disease, acute renal failure, and secondary hyperparathyroidism, as well as vascular dysfunction, atherosclerosis, and cardiovascular morbidity and mortality. We outline and discuss the current commercially available assays for determination of FGF-23 and Klotho and the assay limitations that must be overcome to translate these biomarkers into reliable indicators in clinical practice. SUMMARY In addition to its physiological role, the FGF-23/Klotho system appears to provide important information regarding the pathophysiology of several clinical conditions. Although there has been increasing study of the components of this new biological system and their potential use as clinical biomarkers, the ultimate value of this system in clinical practice will not be known until remaining assay limitations can be overcome and adequately designed studies have been conducted to demonstrate its clinical utility.

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“…It is expressed as a type I transmembrane protein mainly in the distal tubules of kidney epithelial cells as well as in parathyroid cells, adipocytes and vascular endothelial cells. [1][2][3] Membrane-bound α-klotho is shed from the cell surface by proteolytic cleavage and circulates in the blood as a hormone. 4,5 Clinical studies have suggested that circulating α-klotho was a potential reno-protective factor in chronic kidney disease (CKD).…”

Section: Introductionmentioning

confidence: 99%

Elevated circulating alpha-klotho by angiotensin II receptor blocker losartan is associated with reduction of albuminuria in type 2 diabetic patients

Lim

Liu

Tavintharan

et al. 2013

J Renin Angiotensin Aldosterone Syst

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Introduction:The aging-suppression gene α-klotho is potentially reno-protective. Animal studies suggest that angiotensin II may be a negative regulator of α-klotho expression. Therefore, we hypothesize that renin-angiotensin system antagonism may increase α-klotho secretion in type 2 diabetes (T2DM). Subjects and methods:In this post-hoc analysis of a randomized crossover study, 33 T2DM subjects with albuminuria received either 50 mg of losartan or 20 mg of quinapril (both 50% maximal dose) daily for 4 weeks with 4-week washout period in between. Results: Our data showed that losartan, but not quinapril, significantly increased circulating α-klotho level by an average of 23% (from 542 pg/ml to 668 pg/ml, p=0.001). Linear regression revealed that, besides different mode of treatment, increment in plasma α-klotho was associated with decrement in urine albumin/creatinine ratio (β=-0.263, p=0.029). Conclusions: The angiotensin receptor blocker losartan increases circulating α-klotho in T2DM with albuminuria. The clinical significance of this rise in α-klotho associated with losartan intervention deserves further investigation.

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Expression of FGF23/KLOTHO system in human vascular tissue

Cited by 106 publications

References 35 publications

FGF-23 and the Progression of Coronary Arterial Calcification in Patients New to Dialysis

FGF-23 and the Progression of Coronary Arterial Calcification in Patients New to Dialysis

Pathophysiological Implications of Fibroblast Growth Factor-23 and Klotho and Their Potential Role as Clinical Biomarkers

Elevated circulating alpha-klotho by angiotensin II receptor blocker losartan is associated with reduction of albuminuria in type 2 diabetic patients

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