10.3389/fphys.2019.00986.s002
Fabiola Bonezzi
Fabiola
Bonezzi
Marco Piccoli
Marco
Piccoli
Michele Dei Cas
Michele Dei
Cas
Rita Paroni
Rita
Paroni
Alessandra Mingione
Alessandra
Mingione
Michelle M. Monasky
Michelle M.
Monasky
Anna Caretti
Anna
Caretti
Chiara Riganti
Chiara
Riganti
Riccardo Ghidoni
Riccardo
Ghidoni
Carlo Pappone
Carlo
Pappone
Luigi Anastasia
Luigi
Anastasia
Paola Signorelli
Paola
Signorelli
Image_2_Sphingolipid Synthesis Inhibition by Myriocin Administration Enhances Lipid Consumption and Ameliorates Lipid Response to Myocardial Ischemia Reperfusion Injury.eps
Frontiers
2019
sphingolipids
ceramide
myriocin
ischemia
reperfusion
metabolism
2019-08-09 13:04:52
Figure
https://frontiersin.figshare.com/articles/figure/Image_2_Sphingolipid_Synthesis_Inhibition_by_Myriocin_Administration_Enhances_Lipid_Consumption_and_Ameliorates_Lipid_Response_to_Myocardial_Ischemia_Reperfusion_Injury_eps/9439604
<p>Myocardial infarct requires prompt thrombolytic therapy or primary percutaneous coronary intervention to limit the extent of necrosis, but reperfusion creates additional damage. Along with reperfusion, a maladaptive remodeling phase might occur and it is often associated with inflammation, oxidative stress, as well as a reduced ability to recover metabolism homeostasis. Infarcted individuals can exhibit reduced lipid turnover and their accumulation in cardiomyocytes, which is linked to a deregulation of peroxisome proliferator activated receptors (PPARs), controlling fatty acids metabolism, energy production, and the anti-inflammatory response. We previously demonstrated that Myriocin can be effectively used as post-conditioning therapeutic to limit ischemia/reperfusion-induced inflammation, oxidative stress, and infarct size, in a murine model. In this follow-up study, we demonstrate that Myriocin has a critical regulatory role in cardiac remodeling and energy production, by up-regulating the transcriptional factor EB, PPARs nuclear receptors and genes involved in fatty acids metabolism, such as VLDL receptor, Fatp1, CD36, Fabp3, Cpts, and mitochondrial FA dehydrogenases. The overall effects are represented by an increased β–oxidation, together with an improved electron transport chain and energy production. The potent immunomodulatory and metabolism regulatory effects of Myriocin elicit the molecule as a promising pharmacological tool for post-conditioning therapy of myocardial ischemia/reperfusion injury.</p>