5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside Increases Myocardial Glucose Uptake during Reperfusion and Induces Late Pre-conditioning: Potential Role of AMP-Activated Protein Kinase

Kristiansen, Steen Buus; Solskov, Lasse; Jessen, Niels; Løfgren, Bo; Schmitz, Ole; Nielsen‐Kudsk, Jens Erik; Nielsen, Thomas; Bøtker, Hans Erik; Lund, Sten

doi:10.1111/j.1742-7843.2009.00402.x

Cited by 18 publications

(13 citation statements)

References 47 publications

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“…We found that infarct size in aged animals was relatively small (∼12%) (as previously reported [2]) and AICAR treatment did not alter infarct size or area at risk (Supplemental Figure 4B). Despite the fact that ischemia itself markedly activates AMPK, it has been demonstrated in isolated reperfused hearts that AICAR reduces infarct size in young animals [40-42]. In this study the role of AICAR does not appear to relate to myocardial infarction size; moreover, there is no apparent AICAR effect seen in the first week of infarction (AICAR treatment ceased 5 days post-MI).…”

Section: Discussionmentioning

confidence: 57%

AICAR-dependent AMPK activation improves scar formation in the aged heart in a murine model of reperfused myocardial infarction

Cieslik

Taffet

Crawford

et al. 2013

Journal of Molecular and Cellular Cardiology

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We have demonstrated that scar formation after myocardial infarction (MI) is associated with an endogenous pool of CD44posCD45neg multipotential mesenchymal stem cells (MSC). MSC differentiate into fibroblasts secreting collagen that forms a scar and mature into myofibroblasts that express alpha smooth muscle actin (α-SMA) that stabilizes the scar. In the aging mouse, cardiac repair after MI is associated with impaired differentiation of MSC; MSC derived from aged hearts form dysfunctional fibroblasts that deposit less collagen in response to transforming growth factor beta-1 (TGF-β1) and poorly mature into myofibroblasts. We found in vitro that the defect in myofibroblast maturation can be remedied by AICAR, which activates non-canonical TGF-β signaling through AMP-activated protein kinase (AMPK). In the present study, we injected aged mice with AICAR and subjected them to 1h occlusion of the left anterior descending artery (LAD) and then reperfusion for up to 30 days. AICAR-dependent AMPK signaling led to mobilization of an endogenous CD44posCD45neg MSC and its differentiation towards fibroblasts and myofibroblasts in the infarct. This was accompanied by enhanced collagen deposition and collagen fiber maturation in the scar. The AICAR-treated group has demonstrated reduced adverse remodeling as indicated by improved apical end diastolic dimension but no changes in ejection fraction and cardiac output were observed. We concluded that these data indicate the novel, previously not described role of AMPK in the post-MI scar formation. These findings can potentially lead to a new therapeutic strategy for prevention of adverse remodeling in the aging heart.

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Section: Discussionmentioning

confidence: 57%

AICAR-dependent AMPK activation improves scar formation in the aged heart in a murine model of reperfused myocardial infarction

Cieslik

Taffet

Crawford

et al. 2013

Journal of Molecular and Cellular Cardiology

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“…AMPK is believed to be quiescent in the heart when energy supply-demand is in balance, but is activated during changing metabolic conditions (such as exercise or ischemia; reviewed in 4 and 66). Pharmacological activation of AMPK has been shown to reduce infarct size to a similar degree as exercise preconditioning (69). Cardiac AMPK is activated following treadmill running, with the AMPK␣-2 isoform appearing to be the most responsive (30,69,95).…”

Section: How Much Exercise Is Needed To Protect the Heart?mentioning

confidence: 99%

“…Pharmacological activation of AMPK has been shown to reduce infarct size to a similar degree as exercise preconditioning (69). Cardiac AMPK is activated following treadmill running, with the AMPK␣-2 isoform appearing to be the most responsive (30,69,95). Relating to the cardioprotective mechanism of action, AMPK activation is postulated to stimulate glucose/fat metabolism in the heart during metabolic stress (4,66), and may promote translocation of cardiac ATP-sensitive potassium channel subunits (123; described in more detail below).…”

Section: How Much Exercise Is Needed To Protect the Heart?mentioning

confidence: 99%

Exercise-induced cardiac preconditioning: how exercise protects your achy-breaky heart

Frasier

Moore

Brown

2011

Journal of Applied Physiology

102

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The ability of exercise to protect the heart against ischemia-reperfusion (I/R) injury is well known in both human epidemiological studies and experimental animal models. In this review article, we describe what is currently known about the ability of exercise to precondition the heart against infarction. Just 1 day of exercise can protect the heart against ischemia/reperfusion damage, and this protection is upheld with months of exercise, making exercise one of the few sustainable preconditioning stimuli. Exercise preconditioning depends on the model and intensity of exercise, and appears to involve heightened oxidant buffering capacity, upregulated subunits of sarcolemmal ATP-sensitive potassium channels, and adaptations to cardiac mitochondria. We review the putative mechanisms involved in exercise preconditioning and point out many areas where future research is necessary to advance our understanding of how this stimulus confers resistance against I/R damage.

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“…and AICAR (0.7 mg/g i.p.) 12 h before IRI) [11]. ; (v) melatonin + rapamycin group (treated with melatonin (20 mg/kg i.p.)…”

Section: Methodsmentioning

confidence: 99%

Melatonin Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Autophagy Via an AMPK/mTOR Signaling Pathway

Chen

Liu

Chen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Melatonin has been demonstrated to protect cardiac microvascular endothelial cells (CMECs) against ischemia/reperfusion injury (IRI). Autophagy plays different roles in the heart during ischemia and reperfusion. The AMP activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway is associated with autophagy. This study sought to explore whether melatonin regulates CMEC autophagy through the AMPK/mTOR signaling pathway. Methods: The effects of melatonin in IRI were investigated in vivo rat models and in vitro neonatal CMECs. Myocardial infarct size was achieved by Evans blue and triphenyltetrazolium chloride staining. The severity of cell injury was evaluated by cell vitality and lactate dehydrogenase (LDH) release assays, and autophagy was evaluated by transmission electron microscopy and the assessment of autophagy-related gene expression, such as that of Beclin 1 and light chain 3-II. Results: In vivo, melatonin markedly reduced infarcted area, improved cardiac function and decreased LDH release. However, the AMPK activator AICAR and the mTOR inhibitor rapamycin reduced the protective effects of melatonin on IRI. In vitro, Beclin1 and light chain 3-II protein were found to be down-regulated and autophagosomes were found to be reduced in response to melatonin, together with an increase in cell vitality and a decrease in LDH. Treatment with AICAR or rapamycin ablated the benefit observed with melatonin treatment. Conclusions: Melatonin played an important and protective role in CMECs by inhibiting autophagy against IRI via the AMPK/mTOR system.

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5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside Increases Myocardial Glucose Uptake during Reperfusion and Induces Late Pre-conditioning: Potential Role of AMP-Activated Protein Kinase

Cited by 18 publications

References 47 publications

AICAR-dependent AMPK activation improves scar formation in the aged heart in a murine model of reperfused myocardial infarction

AICAR-dependent AMPK activation improves scar formation in the aged heart in a murine model of reperfused myocardial infarction

Exercise-induced cardiac preconditioning: how exercise protects your achy-breaky heart

Melatonin Attenuates Myocardial Ischemia/Reperfusion Injury by Inhibiting Autophagy Via an AMPK/mTOR Signaling Pathway

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