AMPK is associated with the beneficial effects of antidiabetic agents on cardiovascular diseases

Lu, Qiongshi; Li, Xuan; Liu, Jia; Sun, Xiaodong; Rousselle, Thomas; Ren, Di; Tong, Nanwei; Li, Ji

doi:10.1042/bsr20181995

Cited by 52 publications

(34 citation statements)

References 171 publications

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“…Studies showed that AMPK deletion promoted mitochondrial fragmentation in ECs by inhibiting the autophagy-dependent degradation of DRP1 [ 105 ]. Numerous anti-diabetic agents may improve endothelial function by targeting AMPK to impact mitochondrial dynamics [ 227 ]. Clusterin, which exerts beneficial effects in ECs under diabetic conditions (both type 1 and type 2), inhibits mitochondrial fragmentation while activating AMPK [ 228 ].…”

Section: Cardio-metabolic Diseasesmentioning

confidence: 99%

AMPK, Mitochondrial Function, and Cardiovascular Disease

Zou

2020

IJMS

138

101

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Adenosine monophosphate-activated protein kinase (AMPK) is in charge of numerous catabolic and anabolic signaling pathways to sustain appropriate intracellular adenosine triphosphate levels in response to energetic and/or cellular stress. In addition to its conventional roles as an intracellular energy switch or fuel gauge, emerging research has shown that AMPK is also a redox sensor and modulator, playing pivotal roles in maintaining cardiovascular processes and inhibiting disease progression. Pharmacological reagents, including statins, metformin, berberine, polyphenol, and resveratrol, all of which are widely used therapeutics for cardiovascular disorders, appear to deliver their protective/therapeutic effects partially via AMPK signaling modulation. The functions of AMPK during health and disease are far from clear. Accumulating studies have demonstrated crosstalk between AMPK and mitochondria, such as AMPK regulation of mitochondrial homeostasis and mitochondrial dysfunction causing abnormal AMPK activity. In this review, we begin with the description of AMPK structure and regulation, and then focus on the recent advances toward understanding how mitochondrial dysfunction controls AMPK and how AMPK, as a central mediator of the cellular response to energetic stress, maintains mitochondrial homeostasis. Finally, we systemically review how dysfunctional AMPK contributes to the initiation and progression of cardiovascular diseases via the impact on mitochondrial function.

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Section: Cardio-metabolic Diseasesmentioning

confidence: 99%

AMPK, Mitochondrial Function, and Cardiovascular Disease

Zou

2020

IJMS

138

101

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“…AMPK activation furthermore reduces hepatic lipogenesis and increases hepatic β-oxidation and reduces adipocyte lipolysis and lipogenesis, which has made it an attractive drug target for the treatment of type 2 diabetes [50]. Despite its obvious regulation of lipid metabolism in the liver and adipose tissue, AMPK activation has been specifically associated with the beneficial effects of some anti-diabetic drugs on cardiovascular diseases [51]. In addition, AMPK activation has been proposed as a therapeutic target in heart failure [52], where its cardioprotective role is thought to be due to mechanisms beyond regulation of cellular energy metabolism [53].…”

Section: Structure and Function Of Ampkmentioning

confidence: 99%

The Role of AMPK Activation for Cardioprotection in Doxorubicin-Induced Cardiotoxicity

Timm

Tyler

2020

Cardiovasc Drugs Ther

124

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Doxorubicin is a commonly used chemotherapeutic agent for the treatment of a range of cancers, but despite its success in improving cancer survival rates, doxorubicin is cardiotoxic and can lead to congestive heart failure. Therapeutic options for this patient group are limited to standard heart failure medications with the only drug specific for doxorubicin cardiotoxicity to reach FDA approval being dexrazoxane, an iron-chelating agent targeting oxidative stress. However, dexrazoxane has failed to live up to its expectations from preclinical studies while also bringing up concerns about its safety. Despite decades of research, the molecular mechanisms of doxorubicin cardiotoxicity are still poorly understood and oxidative stress is no longer considered to be the sole evil. Mitochondrial impairment, increased apoptosis, dysregulated autophagy and increased fibrosis have also been shown to be crucial players in doxorubicin cardiotoxicity. These cellular processes are all linked by one highly conserved intracellular kinase: adenosine monophosphate-activated protein kinase (AMPK). AMPK regulates mitochondrial biogenesis via PGC1α signalling, increases oxidative mitochondrial metabolism, decreases apoptosis through inhibition of mTOR signalling, increases autophagy through ULK1 and decreases fibrosis through inhibition of TGFβ signalling. AMPK therefore sits at the control point of many mechanisms shown to be involved in doxorubicin cardiotoxicity and cardiac AMPK signalling itself has been shown to be impaired by doxorubicin. In this review, we introduce different agents known to activate AMPK (metformin, statins, resveratrol, thiazolidinediones, AICAR, specific AMPK activators) as well as exercise and dietary restriction, and we discuss the existing evidence for their potential role in cardioprotection from doxorubicin cardiotoxicity.

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“…AMPK, which is widely distributed in various cells and organs as a heterotrimeric protein complex, consists of 3 subunits including catalytic α (66kDa) subunits, regulatory β (38 kDa) and γ (38 kDa) subunits which occur as multiple isoforms (α1/α 2; β1/β2; γ1/γ2/γ3) encoded by distinct genes [8]. Compelling evidence has indicated that activated AMPK ameliorates myocardial ischemiareperfusion injury (IRI) [8][9][10]. while the absence of AMPK may promote IRI in an aged heart [11].…”

Section: Introductionmentioning

confidence: 99%

Targeting AMP-Activated Protein Kinase in Aging-Related Cardiovascular Diseases

Tian¹,

Ma²,

Yin³

et al. 2020

Aging and disease

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Aging is a pivotal risk factor for developing cardiovascular diseases (CVD) due to the lifelong exposure to various risk factors that may affect the heart and vasculature during aging. AMP-activated protein kinase (AMPK), a serine/threonine protein kinase, is a pivotal endogenous energy regulator that protects against various pathological alterations. In this report, we first introduced the protective mechanisms of AMPK signaling in myocardium, such as oxidative stress, apoptosis, inflammation, autophagy and inflammatory response. Next, we introduced the potential correlation between AMPK and cardiac aging. Then, we highlighted the roles of AMPK signaling in cardiovascular diseases, including myocardial ischemia, cardiomyopathy, and heart failure. Lastly, some potential directions and further perspectives were expanded. The information extends our understanding on the protective roles of AMPK in myocardial aging, which may contribute to the design of drug targets and sheds light on potential treatments of AMPK for aging-related CVD.

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AMPK is associated with the beneficial effects of antidiabetic agents on cardiovascular diseases

Cited by 52 publications

References 171 publications

AMPK, Mitochondrial Function, and Cardiovascular Disease

AMPK, Mitochondrial Function, and Cardiovascular Disease

The Role of AMPK Activation for Cardioprotection in Doxorubicin-Induced Cardiotoxicity

Targeting AMP-Activated Protein Kinase in Aging-Related Cardiovascular Diseases

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