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.

Sphingolipid synthesis inhibition by myriocin administration enhances lipid consumption and ameliorates lipid response to myocardial ischemia reperfusion injury / F. Bonezzi, M. Piccoli, M. Dei Cas, R. Paroni, A. Mingione, M.M. Monasky, A. Caretti, C. Riganti, R. Ghidoni, C. Pappone, L. Anastasia, P. Signorelli. - In: FRONTIERS IN PHYSIOLOGY. - ISSN 1664-042X. - 10:JUL(2019 Aug 09).

Sphingolipid synthesis inhibition by myriocin administration enhances lipid consumption and ameliorates lipid response to myocardial ischemia reperfusion injury

F. Bonezzi
Co-primo
Investigation
;
M. Piccoli
Co-primo
Investigation
;
M. Dei Cas
Formal Analysis
;
R. Paroni
Writing – Review & Editing
;
A. Mingione
Investigation
;
A. Caretti
Writing – Review & Editing
;
R. Ghidoni
Supervision
;
L. Anastasia
Penultimo
Writing – Review & Editing
;
P. Signorelli
Ultimo
Writing – Review & Editing
2019-08-09

Abstract

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.
Ceramide; Ischemia; Metabolism; Myriocin; Reperfusion; Sphingolipids
Settore BIO/10 - Biochimica
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
Article (author)
File in questo prodotto:
File Dimensione Formato  
129-Sphingolipids synthesis inhibition.pdf

accesso aperto

Descrizione: Articolo principale
Tipologia: Publisher's version/PDF
Dimensione 391.9 kB
Formato Adobe PDF
391.9 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/684623
Citazioni
  • ???jsp.display-item.citation.pmc??? 6
  • Scopus 12
  • ???jsp.display-item.citation.isi??? 12
social impact