Trehalose-Induced Activation of Autophagy Improves Cardiac Remodeling After Myocardial Infarction

Sebastiano Sciarretta, Derek Yee, Narayani Nagarajan, Franca Bianchi, Toshiro Saito, Valentina Valenti, Mingming Tong, Dominic P. Del Re, Carmine Vecchione, Leonardo Schirone, Maurizio Forte, Speranza Rubattu, Akihiro Shirakabe, V. Subbarao Boppana, Massimo Volpe, Giacomo Frati, Peiyong Zhai, Junichi Sadoshima

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

Background: Trehalose (TRE) is a natural, nonreducing disaccharide synthesized by lower organisms. TRE exhibits an extraordinary ability to protect cells against different kinds of stresses through activation of autophagy. However, the effect of TRE on the heart during stress has never been tested. Objectives: This study evaluated the effects of TRE administration in a mouse model of chronic ischemic remodeling. Methods: Wild-type (WT) or beclin 1+/− mice were subjected to permanent ligation of the left anterior descending artery (LAD) and then treated with either placebo or trehalose (1 mg/g/day intraperitoneally for 48 h, then 2% in the drinking water). After 4 weeks, echocardiographic, hemodynamic, gravimetric, histological, and biochemical analyses were conducted. Results: TRE reduced left ventricular (LV) dilation and increased ventricular function in mice with LAD ligation compared with placebo. Sucrose, another nonreducing disaccharide, did not exert protective effects during post-infarction LV remodeling. Trehalose administration to mice overexpressing GFP-tagged LC3 significantly increased the number of GFP-LC3 dots, both in the presence and absence of chloroquine administration. TRE also increased cardiac LC3-II levels after 4 weeks following myocardial infarction (MI), indicating that it induced autophagy in the heart in vivo. To evaluate whether TRE exerted beneficial effects through activation of autophagy, trehalose was administered to beclin 1+/− mice. The improvement of LV function, lung congestion, cardiac remodeling, apoptosis, and fibrosis following TRE treatment observed in WT mice were all significantly blunted in beclin 1+/− mice. Conclusions: TRE reduced MI-induced cardiac remodeling and dysfunction through activation of autophagy.

Original languageEnglish
Pages (from-to)1999-2010
Number of pages12
JournalJournal of the American College of Cardiology
Volume71
Issue number18
DOIs
StatePublished - May 8 2018
Externally publishedYes

Keywords

  • autophagy
  • cardiac remodeling
  • heart failure
  • trehalose
  • ventricular function

Fingerprint Dive into the research topics of 'Trehalose-Induced Activation of Autophagy Improves Cardiac Remodeling After Myocardial Infarction'. Together they form a unique fingerprint.

Cite this