The cardioprotective effects of carvedilol on ischemia and reperfusion injury by AMPK signaling pathway

Hu, Haiyan; Li, Xuan; Ren, Di; Tan, Yi; Chen, Jimei; Yang, Lei; Chen, Ruiping; Li, Ji; Zhu, Ping

doi:10.1016/j.biopha.2019.109106

Cited by 35 publications

(24 citation statements)

References 29 publications

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“…Carvedilol, a third-generation β blocker, is in clinical use for heart failure patients. Carvedilol modulates cardiac AMPK signaling to reduce ischemic insults by I/R [ 182 ]. Treatment of cardiomyocytes with carvedilol augmented phosphorylation of AMPK and its downstream substrate ACC, and ameliorated hypoxia-induced impairment [ 182 ].…”

Section: Ampk Mitochondrial Function and Cvdsmentioning

confidence: 99%

“…Carvedilol modulates cardiac AMPK signaling to reduce ischemic insults by I/R [ 182 ]. Treatment of cardiomyocytes with carvedilol augmented phosphorylation of AMPK and its downstream substrate ACC, and ameliorated hypoxia-induced impairment [ 182 ]. Importantly, carvedilol treatment improved calcium homeostasis with rescuing the peak Ca 2+ signal, the maximum rate of Ca 2+ change during contraction and relaxation under hypoxia conditions [ 182 ].…”

Section: Ampk Mitochondrial Function and Cvdsmentioning

confidence: 99%

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AMPK, Mitochondrial Function, and Cardiovascular Disease

Zou

2020

IJMS

153

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: Ampk Mitochondrial Function and Cvdsmentioning

confidence: 99%

Section: Ampk Mitochondrial Function and Cvdsmentioning

confidence: 99%

AMPK, Mitochondrial Function, and Cardiovascular Disease

Zou

2020

IJMS

153

101

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“…Therefore, a role of AMPK in hypoxic adaptation seems logical. Indeed, there has been increasing evidence of activation of AMPK acting protectively in hypoxia-associated pathologies, e.g., ischemic injury in heart, brain or guts [26][27][28][29]. By decreasing the cellular ATP consumption, the oxygen demand is also lowered; thus, cellular survival is enhanced [30,31].…”

Section: The Role Of Ampk Under Hypoxiamentioning

confidence: 99%

Activation of AMPK under Hypoxia: Many Roads Leading to Rome

Dengler

2020

IJMS

100

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AMP-activated protein kinase (AMPK) is known as a pivotal cellular energy sensor, mediating the adaptation to low energy levels by deactivating anabolic processes and activating catabolic processes in order to restore the cellular ATP supply when the cellular AMP/ATP ratio is increased. Besides this well-known role, it has also been shown to exert protective effects under hypoxia. While an insufficient supply with oxygen might easily deplete cellular energy levels, i.e., ATP concentration, manifold other mechanisms have been suggested and are heavily disputed regarding the activation of AMPK under hypoxia independently from cellular AMP concentrations. However, an activation of AMPK preceding energy depletion could induce a timely adaptation reaction preventing more serious damage. A connection between AMPK and the master regulator of hypoxic adaptation via gene transcription, hypoxia-inducible factor (HIF), has also been taken into account, orchestrating their concerted protective action. This review will summarize the current knowledge on mechanisms of AMPK activation under hypoxia and its interrelationship with HIF.

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“… 157 Angiotensin receptor blockers have been noted to promote autophagy, 158 effects that have been attributed to their effects to activate AMPK and inhibit Akt/mTOR. 159 , 160 Beta-blockade is accompanied by up-regulation of AMPK, 161 , 162 and carvedilol up-regulates PGC-1α 163 and appears to enhance autophagic flux through SIRT1 stimulation 164 and by mTOR inhibition. 165 Spironolactone activates SIRT1/AMPK in the heart, 166 and its action to inhibit Akt/mTOR signalling has been linked to its effect to promote autophagic flux.…”

Section: Importance Of Longevity Gene Signalling and Autophagy Modulamentioning

confidence: 99%

Longevity genes, cardiac ageing, and the pathogenesis of cardiomyopathy: implications for understanding the effects of current and future treatments for heart failure

Packer

2020

European Heart Journal

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The two primary molecular regulators of lifespan are sirtuin-1 (SIRT1) and mammalian target of rapamycin complex 1 (mTORC1). Each plays a central role in two highly interconnected pathways that modulate the balance between cellular growth and survival. The activation of SIRT1 [along with peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α) and adenosine monophosphate-activated protein kinase (AMPK)] and the suppression of mTORC1 (along with its upstream regulator, Akt) act to prolong organismal longevity and retard cardiac ageing. Both activation of SIRT1/PGC-1α and inhibition of mTORC1 shifts the balance of cellular priorities so as to promote cardiomyocyte survival over growth, leading to cardioprotective effects in experimental models. These benefits may be related to direct actions to modulate oxidative stress, organellar function, proinflammatory pathways, and maladaptive hypertrophy. In addition, a primary shared benefit of both SIRT1/PGC-1α/AMPK activation and Akt/mTORC1 inhibition is the enhancement of autophagy, a lysosome-dependent degradative pathway, which clears the cytosol of dysfunctional organelles and misfolded proteins that drive the ageing process by increasing oxidative and endoplasmic reticulum stress. Autophagy underlies the ability of SIRT1/PGC-1α/AMPK activation and Akt/mTORC1 suppression to extend lifespan, mitigate cardiac ageing, alleviate cellular stress, and ameliorate the development and progression of cardiomyopathy; silencing of autophagy genes abolishes these benefits. Loss of SIRT1/PGC-1α/AMPK function or hyperactivation of Akt/mTORC1 is a consistent feature of experimental cardiomyopathy, and reversal of these abnormalities mitigates the development of heart failure. Interestingly, most treatments that have been shown to be clinically effective in the treatment of chronic heart failure with a reduced ejection fraction have been reported experimentally to exert favourable effects to activate SIRT1/PGC-1α/AMPK and/or suppress Akt/mTORC1, and thereby, to promote autophagic flux. Therefore, the impairment of autophagy resulting from derangements in longevity gene signalling is likely to represent a seminal event in the evolution and progression of cardiomyopathy.

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The cardioprotective effects of carvedilol on ischemia and reperfusion injury by AMPK signaling pathway

Cited by 35 publications

References 29 publications

AMPK, Mitochondrial Function, and Cardiovascular Disease

AMPK, Mitochondrial Function, and Cardiovascular Disease

Activation of AMPK under Hypoxia: Many Roads Leading to Rome

Longevity genes, cardiac ageing, and the pathogenesis of cardiomyopathy: implications for understanding the effects of current and future treatments for heart failure

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