Format

Send to

Choose Destination
J Am Coll Cardiol. 2018 May 8;71(18):1999-2010. doi: 10.1016/j.jacc.2018.02.066.

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

Author information

1
Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy; Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Italy.
2
Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark, New Jersey.
3
Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Italy.
4
Department of Imaging, Bambino Gesù Children Hospital, IRCCS, Rome, Italy.
5
Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Italy; University of Salerno, Medicine and Surgery, Baronissi, Italy.
6
Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.
7
Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Italy; Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.
8
Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark, New Jersey. Electronic address: sadoshju@njms.rutgers.edu.

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 beclin1+/- 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.

KEYWORDS:

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

PMID:
29724354
DOI:
10.1016/j.jacc.2018.02.066

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center