Fibroblast growth factor 21 deletion aggravates diabetes-induced pathogenic changes in the aorta in type 1 diabetic mice

Yan, Xiaoqing; Chen, Jun; Zhang, Chi; Zeng, Jun; Zhou, Shanshan; Zhang, Zhiguo; Lu, Xuemian; Chen, Jing; Feng, Wenke; Li, Xiaokun; Tan, Yi

doi:10.1186/s12933-015-0241-0

Cited by 19 publications

(20 citation statements)

References 46 publications

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“…The mass of the heart tends to be larger, with deteriorating cardiac function in FGF21 knock-out rats after continuous infusion of isoprenaline [ 21 ]. Moreover, FGF21 were also shown to play an important role in oxidative stress [ 22 ]; FGF21 deletion aggravates aortic remodeling and cell death probably via exacerbation of aortic inflammation and oxidative stress [ 23 ]. In our study, FGF21 can identify left ventricular systolic dysfunction, which may be due to the above-mentioned mechanism.…”

Section: Discussionmentioning

confidence: 99%

Contribution of serum FGF21 level to the identification of left ventricular systolic dysfunction and cardiac death

Shen

Zhang

Pan

et al. 2017

Cardiovasc Diabetol

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AimThe relationship between fibroblast growth factor 21 (FGF21) and cardiovascular disease has been well established in recent studies. This study aimed to investigate the relationship between FGF21 and left ventricular systolic dysfunction and cardiac death.MethodsTwo-dimensional echocardiography was used to measure the left ventricular ejection fraction (LVEF) to estimate left ventricular systolic function. The optimal cutoff of FGF21 for identifying left ventricular systolic dysfunction at baseline was analyzed via receiver operating characteristic (ROC) curves. The identification of different serum levels of FGF21 and their association with cardiac death was analyzed via Kaplan–Meier survival curves. Serum FGF21 level was measured by an enzyme-linked immunosorbent assay kit, and serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level was determined by a chemiluminescent immunoassay.ResultsA total of 253 patients were recruited for this study at baseline. Patients were excluded if they lacked echocardiography or laboratory measurement data, and there were 218 patients enrolled in the final analysis. The average age was 66.32 ± 10.10 years. The optimal cutoff values of FGF21 and NT-pro-BNP for identifying left ventricular systolic dysfunction at baseline were 321.5 pg/mL and 131.3 ng/L, respectively, determined separately via ROC analysis. The areas under the curves were non-significant among FGF21, NT-pro-BNP and FGF21 + NT-pro-BNP as determined by pairwise comparisons. Both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP were independent risk factors for left ventricular systolic dysfunction at baseline (odd ratio (OR) 3.138 [1.037–9.500], P = 0.043, OR 9.207 [2.036–41.643], P = 0.004, separately). Further Kaplan–Meier survival analysis indicated an association between both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP with cardiac death in 5 years [RR 5.000 (1.326–18.861), P = 0.026; RR 9.643 (2.596–35.825), P = 0.009, respectively].ConclusionsSerum FGF21 level was significantly correlated with left ventricular systolic dysfunction at baseline. Patients with higher serum levels of FGF21 tended to suffer greater risks of cardiac death than patients with lower serum levels of FGF21. The identification of FGF21 and its relationship with left ventricular systolic function and cardiac death were non-inferior to NT-pro-BNP.

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Section: Discussionmentioning

confidence: 99%

Contribution of serum FGF21 level to the identification of left ventricular systolic dysfunction and cardiac death

Shen

Zhang

Pan

et al. 2017

Cardiovasc Diabetol

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“…An earlier in vitro study 82 showed impaired eNOS phosphorylation at Ser-1177 and Ser-633 in HUVECs cells under diabetic conditions, which was reverted by FGF21 administration in an AMP-activated protein kinase-dependent manner. In one study, the eNOS phosphorylation of Ser-1177 in FGF21-KO T1D mice was more downregulated than WT diabetic mice, suggesting that FGF21 deficiency may aggravate aortic damage by eNOS activation damage 104 .…”

Section: Introductionmentioning

confidence: 99%

The role of FGF21 in type 1 diabetes and its complications

Zhang¹,

Weng²,

Wang³

et al. 2018

Int. J. Biol. Sci.

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Data from the International Diabetes Federation show that 347 million people worldwide have diabetes, and the incidence is still rising. Although the treatment of diabetes has been advanced, the current therapeutic options and outcomes, e.g. complications, are yet far from ideal. Therefore, an urgent need exists for the development of more effective therapies. Numerous studies have been conducted to establish and confirm whether FGF21 exerts beneficial effects on obesity and diabetes along with its complications. However, most of the studies associated with FGF21 were conducted in the patients with type 2 diabetes. Subsequently, the effect of FGF21 in the prevention or treatment of type 1 diabetes and its complications were also increasingly reported. In this review, we summarize the findings available on the function of FGF21 and the status of FGF21's treatment for type 1 diabetes. Based on the available information, we found that FGF21 exerts a hypoglycemic effect, restores the function of brown fat, and inhibits various complications in type 1 diabetes patients. Although these features are predominantly similar to those observed in the studies that showed the beneficial impact of FGF21 on type 2 diabetes and its complications, there are also certain distinct features and findings that may be of provide important and instructive for us to understand mechanistic insights and further promote the prevention and treatment of type 1 diabetes.

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“…The mass of the heart tends to be larger, with deteriorating cardiac function in FGF21 knock-out rats after continuous infusion of isoprenaline [21]. Moreover, FGF21 were also shown to play an important role in oxidative stress [22]; FGF21 deletion aggravates aortic remodeling and cell death probably via exacerbation of aortic inflammation and oxidative stress [23]. In our study, FGF21 can identify left ventricular systolic dysfunction, which may be due to the abovementioned mechanism.…”

Section: Discussionmentioning

confidence: 50%

Contribution of Serum FGF-21 Level to the Identification of Left Ventricular Systolic Dysfunction and Cardiac Death

Bao¹,

Shen²,

Zhang³

et al. 2018

Diabetes

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Aim: The relationship between fibroblast growth factor 21 (FGF21) and cardiovascular disease has been well established in recent studies. This study aimed to investigate the relationship between FGF21 and left ventricular systolic dysfunction and cardiac death.Methods: Two-dimensional echocardiography was used to measure the left ventricular ejection fraction (LVEF) to estimate left ventricular systolic function. The optimal cutoff of FGF21 for identifying left ventricular systolic dysfunction at baseline was analyzed via receiver operating characteristic (ROC) curves. The identification of different serum levels of FGF21 and their association with cardiac death was analyzed via Kaplan-Meier survival curves. Serum FGF21 level was measured by an enzyme-linked immunosorbent assay kit, and serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level was determined by a chemiluminescent immunoassay.Results: A total of 253 patients were recruited for this study at baseline. Patients were excluded if they lacked echocardiography or laboratory measurement data, and there were 218 patients enrolled in the final analysis. The average age was 66.32 ± 10.10 years. The optimal cutoff values of FGF21 and NT-pro-BNP for identifying left ventricular systolic dysfunction at baseline were 321.5 pg/mL and 131.3 ng/L, respectively, determined separately via ROC analysis. The areas under the curves were non-significant among FGF21, NT-pro-BNP and FGF21 + NT-pro-BNP as determined by pairwise comparisons. Both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP were independent risk factors for left ventricular systolic dysfunction at baseline (odd ratio (OR) 3.138 [1.037-9.500], P = 0.043, OR 9.207 [2.036-41.643], P = 0.004, separately). Further Kaplan-Meier survival analysis indicated an association between both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP with cardiac death in 5 years , P = 0.026; RR 9.643 (2.596-35.825), P = 0.009, respectively].Conclusions: Serum FGF21 level was significantly correlated with left ventricular systolic dysfunction at baseline. Patients with higher serum levels of FGF21 tended to suffer greater risks of cardiac death than patients with lower serum levels of FGF21. The identification of FGF21 and its relationship with left ventricular systolic function and cardiac death were non-inferior to NT-pro-BNP.

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Fibroblast growth factor 21 deletion aggravates diabetes-induced pathogenic changes in the aorta in type 1 diabetic mice

Cited by 19 publications

References 46 publications

Contribution of serum FGF21 level to the identification of left ventricular systolic dysfunction and cardiac death

Contribution of serum FGF21 level to the identification of left ventricular systolic dysfunction and cardiac death

The role of FGF21 in type 1 diabetes and its complications

Contribution of Serum FGF-21 Level to the Identification of Left Ventricular Systolic Dysfunction and Cardiac Death

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