Author + information
- Received May 18, 2017
- Revision received February 15, 2018
- Accepted February 19, 2018
- Published online April 30, 2018.
- Sebastiano Sciarretta, MD, PhDa,b,
- Derek Yee, MDc,
- Narayani Nagarajan, MSc,
- Franca Bianchi, MSb,
- Toshiro Saito, MD, PhDc,
- Valentina Valenti, MDd,
- Mingming Tong, MSc,
- Dominic P. Del Re, PhDc,
- Carmine Vecchione, MDb,e,
- Leonardo Schirone, MSa,
- Maurizio Forte, PhDb,
- Speranza Rubattu, MDb,f,
- Akihiro Shirakabe, MDc,
- V. Subbarao Boppana, MDc,
- Massimo Volpe, MDb,f,
- Giacomo Frati, MDa,b,
- Peiyong Zhai, MD, PhDc and
- Junichi Sadoshima, MD, PhDc,∗ ()
- aDepartment of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy
- bDepartment of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Italy
- cDepartment of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, Newark, New Jersey
- dDepartment of Imaging, Bambino Gesù Children Hospital, IRCCS, Rome, Italy
- eUniversity of Salerno, Medicine and Surgery, Baronissi, Italy
- fDepartment of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy
- ↵∗Address for correspondence:
Dr. Junichi Sadoshima, Department of Cell Biology and Molecular Medicine, Rutgers New Jersey Medical School, 185 South Orange Avenue, Room 1-543, Newark, New Jersey 07103.
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.
Dr. Sciarretta was partially supported by a grant from the Italian Ministry of Health (GR-2013-02355401). Dr. Sadoshima was supported in part by U.S. Public Health Service Grants HL67724, HL91469, HL102738, HL112330, and AG23039 and by the Leducq Foundation Transatlantic Network of Excellence.
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received May 18, 2017.
- Revision received February 15, 2018.
- Accepted February 19, 2018.
- 2018 American College of Cardiology Foundation
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