Reduced scar maturation and contractility lead to exaggerated left ventricular dilation after myocardial infarction in mice lacking AMPKα1

Noppe, Gauthier; Dufeys, Cécile; Buchlin, Patricia; Marquet, Nicolas; Castanares-Zapatero, Diego; Balteau, Magali; Hermida, Nerea; Bouzin, Caroline; Esfahani, Hrag; Viollet, Benoı̂t; Bertrand, Luc; Balligand, Jean‐Luc; Vanoverschelde, Jean-Louis; Beauloye, Christophe; Horman, Sandrine

doi:10.1016/j.yjmcc.2014.04.018

“…Considerable pieces of evidence indicate that AMPK responds to different stimuli and suppresses cardiac fibrosis [43][44][45][46]. Metformin-activated AMPK suppresses the phosphorylation and nuclear translocation of Smad3 in response to TGF-β1 and inhibits cardiac fibrosis and collagen synthesis in CFs [46].…”

Section: Discussionmentioning

confidence: 99%

CTRP3 attenuates post-infarct cardiac fibrosis by targeting Smad3 activation and inhibiting myofibroblast differentiation

Wu

¹

,

Lei

²

,

Wang

³

et al. 2015

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“…In other studies, it has been established that metformin inhibits myofibroblast differentiation by suppressing ROS generation via the inhibition of the NADPH oxidase pathway (Bai et al, 2013), AMPK probably mediating this effect. Of note, a genetic link between AMPK and cardiac fibrosis has been recently demonstrated in a myocardial infarction mouse model (Noppe et al, 2014).…”

Section: Metformin In Cardiac Fibrosismentioning

confidence: 98%

Metformin: From Mechanisms of Action to Therapies

Foretz

¹

,

Guigas

²

,

Bertrand

³

et al. 2014

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Metformin is currently the first-line drug treatment for type 2 diabetes. Besides its glucose-lowering effect, there is interest in actions of the drug of potential relevance to cardiovascular diseases and cancer. However, the underlying mechanisms of action remain elusive. Convincing data place energy metabolism at the center of metformin's mechanism of action in diabetes and may also be of importance in cardiovascular diseases and cancer. Metformin-induced activation of the energy-sensor AMPK is well documented, but may not account for all actions of the drug. Here, we summarize current knowledge about the different AMPK-dependent and AMPK-independent mechanisms underlying metformin action.

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“…Luc Bertrand (Université Catholique de Louvain) described new molecular mechanisms and AMPK downstream targets involved in its insulin-sensitizing and antihypertrophic actions. Sandrine Horman (Université Catholique de Louvain) presented evidence that AMPKa1 plays a critical role in in cardiac fibroblast/myofibroblast biology, providing new perspectives and potential therapeutic approaches that could counter the adverse left ventricular remodeling of infarcted hearts (Noppe et al, 2014).…”

Section: Novel Regulatory Mechanisms In Cardiac and Skeletal Muscle Mmentioning

confidence: 99%

“…Luc Bertrand (Université Catholique de Louvain) described new molecular mechanisms and AMPK downstream targets involved in its insulin-sensitizing and antihypertrophic actions. Sandrine Horman (Université Catholique de Louvain) presented evidence that AMPKa1 plays a critical role in in cardiac fibroblast/myofibroblast biology, providing new perspectives and potential therapeutic approaches that could counter the adverse left ventricular remodeling of infarcted hearts (Noppe et al, 2014).Erik Richter and Jorgen Wojtaszewski (both University of Copenhagen) reminded us of the important role of AMPK in skeletal muscle metabolism in response to exercise, in terms of both glucose uptake and fatty acid oxidation. Erik Richter explored the relative role of AMPK and Ca 2+ in increasing glucose uptake during muscle contraction and demonstrated that both metabolic activation of AMPK and Rac1-dependent rearrangement of the actin cytoskeleton, but not Ca 2+ released from the sarcoplasmic reticulum, fully account for contraction-induced muscle glucose transport (Jensen et al, 2014).…”

mentioning

confidence: 99%