scholarly journals Fibroblast Growth Factor 21 Ameliorates NaV1.5 and Kir2.1 Channel Dysregulation in Human AC16 Cardiomyocytes

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiamin Li ◽  
Yuanshi Li ◽  
Yining Liu ◽  
Hang Yu ◽  
Ning Xu ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Ventricular Arrhythmias ◽  
Sodium Current ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Serum Samples

Infarcted myocardium is predisposed to cause lethal ventricular arrhythmias that remain the main cause of death in patients suffering myocardial ischemia. Liver-derived fibroblast growth factor 21 (FGF21) is an endocrine regulator, which exerts metabolic actions by favoring glucose and lipids metabolism. Emerging evidence has shown a beneficial effect of FGF21 on cardiovascular diseases, but the role of FGF21 on ventricular arrhythmias following myocardial infarction (MI) in humans has never been addressed. This study was conducted to investigate the pharmacological effects of FGF21 on cardiomyocytes after MI in humans. Patients with arrhythmia in acute MI and healthy volunteers were enrolled in this study. Serum samples were collected from these subjects on day 1 and days 7–10 after the onset of MI for measuring FGF21 levels using ELISA. Here, we found that the serum level of FGF21 was significantly increased on day 1 after the onset of MI and it returned to normal on days 7–10, relative to the Control samples. In order to clarify the regulation of FGF21 on arrhythmia, two kinds of arrhythmia animal models were established in this study, including ischemic arrhythmia model (MI rat model) and nonischemic arrhythmia model (ouabain-induced guinea pig arrhythmia model). The results showed that the incidence and duration time of ischemic arrhythmias in rhbFGF21-treated MI rats were significantly reduced at different time point after MI compared with normal saline-treated MI rats. Moreover, the onset of the first ventricular arrhythmias was delayed and the numbers of VF and maintenance were attenuated by FGF21 compared to the rhbFGF21-untreated group in the ouabain model. Consistently, in vitro study also demonstrated that FGF21 administration was able to shorten action potential duration (APD) in hydrogen peroxide-treated AC16 cells. Mechanically, FGF21 can ameliorate the electrophysiological function of AC16 cells, which is characterized by rescuing the expression and dysfunction of cardiac sodium current (INa) and inward rectifier potassium (Ik1) in AC16 cells induced by hydrogen peroxide. Moreover, the restorative effect of FGF21 on NaV1.5 and Kir2.1 was eliminated when FGF receptors were inhibited. Collectively, FGF21 has the potential role of ameliorating transmembrane ion channels remodeling through the NaV1.5/Kir2.1 pathway by FGF receptors and thus reducing life-threatening postinfarcted arrhythmias, which provides new strategies for antiarrhythmic therapy in clinics.

Role of Fibroblast growth factor 21 (FGF-21) as a prognostic marker for fetal and maternal complications in patients with gestational diabetes mellitus

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Mohamed Reda Halawa ◽  
Magdy Hassan Kolaib ◽  
Salah Hussein El-Halawany ◽  
Dina Ahmed Marwan ◽  
Ola Mohamed Mostafa Shaheen
Keyword(s):  
Diabetes Mellitus ◽  
Growth Factor ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Fibroblast Growth Factor ◽  
Prognostic Marker ◽  
Diagnostic Marker ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth

Abstract Background Gestational diabetes mellitus (GDM) defined as glucose intolerance with onset or first diagnosis during pregnancy. While GDM usually resolves following delivery, it can have long-lasting health consequences, including increased risk for type 2 diabetes (T2DM) and cardiovascular disease (CVD) in the mother, and future obesity, CVD, T2DM, and/or GDM in the child. This contributes to a vicious intergenerational cycle of obesity and diabetes that impacts the health of the population as a whole. Fibroblast growth factor 21 (FGF21) is a hormone that is expressed predominantly in the liver, but also in other metabolically active tissues such as pancreas, skeletal muscle and adipose tissue. An elevated FGF21 level is also an independent predictor of T2DM. GDM and T2DM are proposed to have similar underlying pathophysiologies, raising the question of whether a similar relationship exists between FGF21 and GDM as it does with T2DM. Objectives assess the role of Fibroblast growth factor 21 (FGF-21) as a prognostic marker for maternal and fetal complications in patients with gestational diabetes mellitus (GDM). Patients and Methods A case control study that was conducted on 50 patients diagnosed with Gestational Diabetes Mellitus and 50 control subjects at Diabetes and Obstetrics outpatient clinic and inpatient ward at Ain Shams university hospitals in the period between December 2018 and July 2019. Patients diagnosed with gestational diabetes mellitus (GDM) at 24-28 weeks of gestation were included in this study. Results FGF 21 levels varied significantly with blood sugar values where higher levels of FGF 21 levels were found in patients with GDM with study results showing that FGF 21 can be used as a diagnostic marker for GDM at levels above 121 pg/ml with sensitivity 84% and specificity 92%. Conclusion FGF 21 can be used as a diagnostic marker for gestational diabetes. Further studies needed for better correlation between FGF 21 levels during pregnancy and maternal outcome.

scholarly journals Fibroblast growth factor-21 serum concentrations are associated with metabolic and hepatic markers in humans

2012 ◽  
Vol 216 (2) ◽  
pp. 135-143 ◽  
Author(s):  
Susan Kralisch ◽  
Anke Tönjes ◽  
Kerstin Krause ◽  
Judit Richter ◽  
Ulrike Lossner ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth ◽  
Serum Concentrations ◽  
The Metabolic Syndrome ◽  
Glutamyl Transferase ◽  
Culture Supernatants

Rather than a traditional growth factor, fibroblast growth factor-21 (FGF21) is considered to be a metabolic hormone. In the current study, we investigated serum FGF21 levels in the self-contained population of Sorbs. Serum FGF21 concentrations were quantified by ELISA and correlated with IGF1 as well as metabolic, renal, hepatic, inflammatory, and cardiovascular parameters in 913 Sorbs from Germany. Moreover, human IGF1 protein secretion was investigated in FGF21-stimulated HepG2 cells. Median FGF21 serum concentrations were 2.1-fold higher in subjects with type 2 diabetes mellitus (141.8 ng/l) compared with controls (66.7 ng/l). Furthermore, nondiabetic subjects with FGF21 levels below the detection limit of the ELISA showed a more beneficial metabolic profile compared with subjects with measurable FGF21. Moreover, FGF21 was significantly lower in female compared with male subjects after adjustment for age and BMI. In multiple regression analyses, circulating FGF21 concentrations remained independently and positively associated with gender, systolic blood pressure, triglycerides, and γ glutamyl transferase whereas a negative association was observed with IGF1 in nondiabetic subjects. Notably, FGF21 significantly inhibited IGF1 secretion into HepG2 cell culture supernatants in preliminary in vitro experiments. FGF21 serum concentrations are associated with facets of the metabolic syndrome, hepatocellular function, as well as GH status.

The role of fibroblast growth factor 21 in the pathogenesis of liver disease: a novel predictor and therapeutic target

2014 ◽  
Vol 18 (11) ◽  
pp. 1305-1313 ◽  
Author(s):  
Wen-Yue Liu ◽  
Sha Huang ◽  
Ke-Qing Shi ◽  
Chen-Chen Zhao ◽  
Li-Li Chen ◽  
...  
Keyword(s):  
Liver Disease ◽  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Therapeutic Target ◽  
Fibroblast Growth Factor 21 ◽  
Fibroblast Growth
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