Fibroblast growth factor 21 inhibited ischemic arrhythmias via targeting miR-143/EGR1 axis

Li, Jiamin; Xu, Chaoqian; Liu, Yining; Li, Yuanshi; Du, Shaowu; Zhang, Ruijie; Sun, Yuehang; Zhang, Ronghao; Wang, Ying; Xue, Hongru; Ni, Sha; Asiya, Mavlikhanova; Xue, Genlong; Li, Yanyao; Shi, Ling; Li, Desheng; Pan, Zhenwei; Zhang, Yong; Wang, Zhiguo; Cai, Benzhi; Wang, Ning; Yang, Baofeng

doi:10.1007/s00395-019-0768-4

Cited by 44 publications

(41 citation statements)

References 44 publications

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“…In high-fat-fed rats, FGF-21 improves left ventricular function, as well as insulin signalling and inflammation [ 344 ]. Several independent studies have shown a protective role of FGF-21 on cardiac hypertrophy [ 345 , 346 , 347 ], and on ventricular arrhythmias in post-infarcted hearts [ 348 ] by reducing inflammation and/or oxidative stress.…”

Section: Role Of Some Adipokines In Inflammatory Processes Associamentioning

confidence: 99%

Adipokines and Inflammation: Focus on Cardiovascular Diseases

Feijóo‐Bandín

Aragón-Herrera

Moraña-Fernández

et al. 2020

IJMS

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It is well established that adipose tissue, apart from its energy storage function, acts as an endocrine organ that produces and secretes a number of bioactive substances, including hormones commonly known as adipokines. Obesity is a major risk factor for the development of cardiovascular diseases, mainly due to a low grade of inflammation and the excessive fat accumulation produced in this state. The adipose tissue dysfunction in obesity leads to an aberrant release of adipokines, some of them with direct cardiovascular and inflammatory regulatory functions. Inflammation is a common link between obesity and cardiovascular diseases, so this review will summarise the role of the main adipokines implicated in the regulation of the inflammatory processes occurring under the scenario of cardiovascular diseases.

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Section: Role Of Some Adipokines In Inflammatory Processes Associamentioning

confidence: 99%

Adipokines and Inflammation: Focus on Cardiovascular Diseases

Feijóo‐Bandín

Aragón-Herrera

Moraña-Fernández

et al. 2020

IJMS

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“…ER stress can act as an adaptive response in cardiomyocytes [ 61 ]. Mild ER stress is characterized by increased intracellular calcium levels, which accelerate calcium-dependent ATP metabolism [ 62 ]. However, excessive ER stress is associated with the activation of CHOP and PERK, transcription factors that promote expression of apoptosis-related genes such as Bax and Bad [ 63 ].…”

Section: Discussionmentioning

confidence: 99%

Bevacizumab‐Induced Mitochondrial Dysfunction, Endoplasmic Reticulum Stress, and ERK Inactivation Contribute to Cardiotoxicity

Tian

Yue

et al. 2021

Oxidative Medicine and Cellular Longevity

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The molecular mechanisms underlying the cardiotoxicity associated with bevacizumab, a first-line immunotherapeutic agent used to treat lung cancer, are not fully understood. Here, we examined intracellular signal transduction in cardiomyocytes after exposure to different doses of bevacizumab in vitro. Our results demonstrated that bevacizumab significantly and dose-dependently reduces cardiomyocyte viability and increases cell apoptosis. Bevacizumab treatment also led to mitochondrial dysfunction in cardiomyocytes, as evidenced by the decreased ATP production, increased ROS production, attenuated antioxidative enzyme levels, and reduced respiratory complex function. In addition, bevacizumab induced intracellular calcium overload, ER stress, and caspase-12 activation. Finally, bevacizumab treatment inhibited the ERK signaling pathway, which, in turn, significantly reduced cardiomyocyte viability and contributed to mitochondrial dysfunction. Together, our results demonstrate that bevacizumab-mediated cardiotoxicity is associated with mitochondrial dysfunction, ER stress, and ERK pathway inactivation. These findings may provide potential treatment targets to attenuate myocardial injury during lung cancer immunotherapy.

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“…Presumably via different downstream effectors that regulate myocyte apoptosis, MEK1 transgenic mice and ERK2 hemizygous knock-out mice exhibit decreased and increased infarct size, respectively, after ischemia-reperfusion (Lips et al, 2004). Likewise, gain and loss of ERK1/2 signaling may explain the beneficial and deleterious effects on myocyte survival and infarct size of exogenous FGF21 and Fgf21 knock-out, respectively, in mice subjected to ischemia-reperfusion injury or permanent coronary artery ligation (Joki et al, 2015;Liu et al, 2013), although other ERK1/2-independent pathways may also be involved (Hu et al, 2018;Li et al, 2020b;Sun et al, 2019). This pro-survival signaling could complicate the targeting of FGF21-FGFR4 signaling in diabetic cardiomyopathy.…”

Section: Discussionmentioning

confidence: 99%

“…Notably, FGF21 expression has been found to be increased in HFpEF patients with diastolic dysfunction (Chou et al, 2016). FGF21 appears to have direct effects on the heart, including cardio-protective actions of short-term FGF21 elevations during ischemia/reperfusion injury, β-adrenergic activation, or hypertension (Hu et al, 2018;Joki et al, 2015;Li et al, 2020b;Li et al, 2019;Liu et al, 2013;Patel et al, 2014;Planavila et al, 2013;Planavila et al, 2015a;Ruan et al, 2018;Sun et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

FGF21-FGFR4 signaling in cardiac myocytes promotes concentric cardiac hypertrophy in mouse models of diabetes

Yanucil

Kentrup

et al. 2021

Preprint

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Fibroblast growth factor (FGF) 21, a hormone that increases insulin sensitivity, has shown promise as a therapeutic agent to improve metabolic dysregulation. Here we report that FGF21 directly targets cardiac myocytes by binding β-klotho and FGF receptor (FGFR) 4. In combination with high glucose, FGF21 induces cardiac myocyte growth in width mediated by extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. While short-term FGF21 elevation can be cardio-protective, we find that in type 2 diabetes (T2D) in mice, where serum FGF21 levels are elevated, FGFR4 activation induces concentric cardiac hypertrophy. As T2D patients are at risk for heart failure with preserved ejection fraction (HFpEF), we propose that induction of concentric hypertrophy by elevated FGF21-FGFR4 signaling constitutes a novel mechanism promoting T2D-associated HFpEF and that FGFR4 blockade might serve as a cardio-protective therapy in T2D. In addition, potential adverse cardiac effects of FGF21 mimetics currently in clinical trials should be investigated.

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Fibroblast growth factor 21 inhibited ischemic arrhythmias via targeting miR-143/EGR1 axis

Cited by 44 publications

References 44 publications

Adipokines and Inflammation: Focus on Cardiovascular Diseases

Adipokines and Inflammation: Focus on Cardiovascular Diseases

Bevacizumab‐Induced Mitochondrial Dysfunction, Endoplasmic Reticulum Stress, and ERK Inactivation Contribute to Cardiotoxicity

FGF21-FGFR4 signaling in cardiac myocytes promotes concentric cardiac hypertrophy in mouse models of diabetes

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