Correlation Between Fibroblast Growth Factor-23 and Pulmonary Arterial Hypertension in Hemodialysis Patients

2021 ◽  
Vol 15 (4) ◽  
Author(s):  
Maryam Miri ◽  
Mahnaz Ahmadi ◽  
Mohsen Hatami
Keyword(s):  
Growth Factor ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Hemodialysis Patients ◽  
Fibroblast Growth ◽  
Pulmonary Arterial

scholarly journals Higher plasma fibroblast growth factor 23 levels are associated with a higher risk profile in pulmonary arterial hypertension

2019 ◽  
Vol 9 (4) ◽  
pp. 204589401989544 ◽  
Author(s):  
Habib Bouzina ◽  
Roger Hesselstrand ◽  
Göran Rådegran
Keyword(s):  
Growth Factor ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Right Atrial ◽  
Walking Distance ◽  
Fibroblast Growth ◽  
Pulmonary Arterial ◽  
Metabolic Biomarkers

Metabolic abnormalities are proposed to contribute to pulmonary arterial as well as right ventricular remodelling in pulmonary arterial hypertension. Among the proposed abnormalities are altered glucose and lipid processing, mitochondrial malfunction, oxidative stress as well as vitamin D and iron abnormalities. In the present study, we investigated 11 metabolic plasma biomarkers, with the hypothesis that metabolic proteins may mirror disease severity in pulmonary arterial hypertension. Using proximity extension assays, plasma metabolic biomarkers were measured in 48 pulmonary arterial hypertension patients at diagnosis and, in 33 of them, at an early treatment follow-up, as well as in 16 healthy controls. Among the studied metabolic biomarkers, plasma fibroblast growth factor-23 ( p < 0.001), fibroblast growth factor-21 ( p < 0.001), fatty acid binding protein 4 ( p < 0.001) and lectin-like oxidised low-density lipoprotein receptor 1 ( p < 0.001) were increased and paraoxonase-3 was decreased ( p < 0.001) in pulmonary arterial hypertension at diagnosis versus controls. Fibroblast growth factor-23 showed the strongest correlations to studied clinical parameters and was therefore selected for further analyses. Fibroblast growth factor-23 correlated specifically to mean right atrial pressure ( r = 0.67, p < 0.001), six-min walking distance ( r = −0.66, p < 0.001), NT-proBNP ( r = 0.64, p < 0.001), venous oxygen saturation ( r = −0.61, p < 0.001), cardiac index ( r = −0.39, p < 0.007) and pulmonary vascular resistance ( r = 0.37, p < 0.01). Fibroblast growth factor-23 correlated moreover to ESC/ERS ( r = 0.72, p < 0.001) and the REVEAL risk score ( r = 0.61, p < 0.001). Comparing early treatment follow-up with baseline, fibroblast growth factor-23 decreased ( p < 0.02), with changes in fibroblast growth factor-23 correlating to changes in six-min walking distance ( r = −0.56, p < 0.003), venous oxygen saturation ( r = −0.46, p < 0.01), pulmonary vascular resistance ( r = 0.43, p < 0.02), mean right atrial pressure ( r = 0.38, p < 0.04) and cardiac index ( r = −0.39, p < 0.04). Elevated plasma fibroblast growth factor-23 levels at pulmonary arterial hypertension diagnosis were associated with worse haemodynamics and a higher risk profile, and were decreased after the administration of pulmonary arterial hypertension-specific treatment.

Elevated Basic Fibroblast Growth Factor Levels in Patients With Pulmonary Arterial Hypertension

CHEST Journal ◽  
2004 ◽  
Vol 126 (4) ◽  
pp. 1255-1261 ◽  
Author(s):  
Jacques I. Benisty ◽  
Vallerie V. McLaughlin ◽  
Michael J. Landzberg ◽  
Jonathan D. Rich ◽  
Jane W. Newburger ◽  
...  
Keyword(s):  
Growth Factor ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Fibroblast Growth ◽  
Pulmonary Arterial

scholarly journals FGF12 (Fibroblast Growth Factor 12) Inhibits Vascular Smooth Muscle Cell Remodeling in Pulmonary Arterial Hypertension

Hypertension ◽  
2020 ◽  
Vol 76 (6) ◽  
pp. 1778-1786
Author(s):  
Yeongju Yeo ◽  
Eunhee S. Yi ◽  
Jeong-Min Kim ◽  
Eun-Kyung Jo ◽  
Songyi Seo ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Fibroblast Growth Factor ◽  
Vascular Remodeling ◽  
Fibroblast Growth ◽  
Pulmonary Vascular Remodeling ◽  
Phenotype Switch ◽  
Pulmonary Arterial

Loss of BMP (bone morphogenic protein) signaling induces a phenotype switch of pulmonary arterial smooth muscle cells (PASMCs), which is the pathological basis of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Here, we identified FGF12 (fibroblast growth factor 12) as a novel regulator of the BMP-induced phenotype change in PASMCs and elucidated its role in pulmonary vascular remodeling during PAH development. Using murine models of PAH and lung specimens of patients with PAH, we observed that FGF12 expression was significantly reduced in PASMCs. In human PASMCs, FGF12 expression was increased by canonical BMP signaling. FGF12 knockdown blocked the antiproliferative and prodifferentiation effect of BMP on human PASMCs, suggesting that FGF12 is required for the BMP-mediated acquisition of the quiescent and differentiated PASMC phenotype. Mechanistically, FGF12 regulated the BMP-induced phenotype change by inducing MEF2a (myocyte enhancer factor 2a) phosphorylation via p38MAPK signaling, thereby modulating the expression of MEF2a target genes involved in cell proliferation and differentiation. Furthermore, we observed that TG (transgenic) mice with smooth muscle cell–specific FGF12 overexpression were protected from chronic hypoxia–induced PAH development, pulmonary vascular remodeling, and right ventricular hypertrophy. Consistent with the in vitro data using human PASMCs, FGF12 TG mice showed increased MEF2a phosphorylation and a substantial change in MEF2a target gene expression, compared with the WT (wild type) controls. Overall, our findings demonstrate a novel BMP/FGF12/MEF2a pathway regulating the PASMC phenotype switch and suggest FGF12 as a potential target for the development of therapeutics for ameliorating pulmonary vascular remodeling in PAH.

Acetate-free biofiltration to remove fibroblast growth factor 23 in hemodialysis patients: a pilot study

2017 ◽  
Vol 31 (3) ◽  
pp. 429-433 ◽  
Author(s):  
Valeria Cernaro ◽  
Silvia Lucisano ◽  
Valeria Canale ◽  
Annamaria Bruzzese ◽  
Daniela Caccamo ◽  
...  
Keyword(s):  
Pilot Study ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Hemodialysis Patients ◽  
Fibroblast Growth

scholarly journals Fibroblast growth factor 23 (FGF23) level is associated with ultrafiltration rate in patients on hemodialysis

2020 ◽  
Author(s):  
Yoko Nishizawa ◽  
Yumi Hosoda ◽  
Ai Horimoto ◽  
Kiyotsugu Omae ◽  
Kyoko Ito ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 23 ◽  
Univariate Analysis ◽  
Hemodialysis Patients ◽  
Left Ventricular ◽  
Fibroblast Growth ◽  
Ultrafiltration Rate ◽  
Dialysis Duration ◽  
The Mean

Abstract Fibroblast growth factor 23 (FGF23) is a bone-derived hormone that regulates renal phosphate reabsorption and vitamin D synthesis in renal proximal tubules. High circulating FGF23 levels are associated with increased mortality in patients with chronic kidney disease and those on dialysis. Current data also suggest higher circulating levels of FGF23 are associated with cardiovascular mortality, vascular calcification, and left ventricular hypertrophy; however, evidence on the role of FGF23 in patients on dialysis is incomplete, and some of the data, especially those on cardiovascular disease (CVD), are controversial. This study aimed to evaluate factors associated with FGF23 in hemodialysis patients with or without CVD. Randomly selected 76 patients on maintenance hemodialysis at a single hemodialysis center were enrolled. After the exclusion of eight patients with extremely outlying FGF23 levels, 68 patients, including 48 males and 46 patients with a CVD history, were included in the study. The mean age was 64.4 ± 12.1 years, and the mean dialysis duration was 12.7 ± 7.1 years. Dialysis duration, time-averaged concentration of urea (TAC-urea), ultrafiltration rate (UFR), blood pressure during hemodialysis session, laboratory data, and echocardiographic parameters including interventricular septum thickness (IVST), left ventricular mass indices (LVMI), and ejection fraction were included in univariate and multivariate analyses. The median lgFGF23 levels in the overall cohort and in those with and without CVD were 2.14 (interquartile range, IQR − 0.43 to − 4.23), 2.01 (− 0.52 to 4.12), and 2.59 (0.07 to 4.32), respectively, and there was no difference between the patients with and without CVD (p = 0.14). The univariate analysis revealed that FGF23 was significantly associated with age (r =  − 0.12, p < 0.01), duration of hemodialysis (r =  − 0.11, p < 0.01), TAC-urea (r = 0.29, p = 0.01), UFR (r = 0.26, p = 0.04), alkaline phosphatase (ALP; r =  − 0.27, p = 0.03), corrected serum calcium (cCa; r = 0.32, p < 0.01), serum phosphate (iP, r = 0.57, p < 0.01), intact parathyroid hormone (iPTH; r = 0.38, p < 0.01), IVST (r = 0.30, p = 0.01), and LVMI (r = 0.26, p = 0.04). In multivariate regression analysis, FGF23 was significantly associated with cCa (F = 25.6, p < 0.01), iP (F = 22.5, p < 0.01), iPTH (F = 19.2, p < 0.01), ALP (F = 5.34, p = 0.03), and UFR (F = 3.94, p = 0.05). In addition, the univariate analysis after the categorization of patients according to CVD indicated that FGF23 was significantly associated with cCa (r = 0.34, p = 0.02), iP (r = 0.41, p < 0.01), iPTH (r = 0.39, p = 0.01), and TAC-urea (r = 0.45, p < 0.01) in patients with CVD, whereas only IVST (r = 0.53, p = 0.04) was associated with FGF23 in those without CVD. FGF23 levels in hemodialysis patients were extremely high and associated not only with mineral bone disease-related factors but also with UFR. Additionally, dialysis efficacy might be associated with lower FGF23 levels in patients with CVD.

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