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 1þ/ mice were subjected to permanent ligation of the left anterior descending artery (LAD) and then treated with either placebo or trehalose (1 mg/g per 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 1þ/ 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 1þ/ mice. CONCLUSIONS TRE reduced MI-induced cardiac remodeling and dysfunction through activation of autophagy.

Trehalose, a Natural Disaccharide, Reduces Cardiac Remodeling After Myocardial Infarction Through Autophagy Activation / Sciarretta, Sebastiano; Yee, Derek; Nagarajan, Narayani; Bianchi, Franca; Saito, Toshiro; Valenti, Valentina; Tong, Mingming; Del Re, Dominic P.; Vecchione, Carmine; Schirone, Leonardo; Forte, Maurizio; Rubattu, Speranza Donatella; Shirakabe, Akihiro; Subbarao Boppana, V.; Volpe, Massimo; Frati, Giacomo; Zhai, Peiyong; Sadoshima, Junichi. - In: JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY. - ISSN 1558-3597. - (In corso di stampa).

Trehalose, a Natural Disaccharide, Reduces Cardiac Remodeling After Myocardial Infarction Through Autophagy Activation.

Sebastiano Sciarretta;Leonardo Schirone;Speranza Rubattu;Massimo Volpe;Giacomo Frati;
In corso di stampa

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 1þ/ mice were subjected to permanent ligation of the left anterior descending artery (LAD) and then treated with either placebo or trehalose (1 mg/g per 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 1þ/ 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 1þ/ mice. CONCLUSIONS TRE reduced MI-induced cardiac remodeling and dysfunction through activation of autophagy.
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Trehalose, a Natural Disaccharide, Reduces Cardiac Remodeling After Myocardial Infarction Through Autophagy Activation / Sciarretta, Sebastiano; Yee, Derek; Nagarajan, Narayani; Bianchi, Franca; Saito, Toshiro; Valenti, Valentina; Tong, Mingming; Del Re, Dominic P.; Vecchione, Carmine; Schirone, Leonardo; Forte, Maurizio; Rubattu, Speranza Donatella; Shirakabe, Akihiro; Subbarao Boppana, V.; Volpe, Massimo; Frati, Giacomo; Zhai, Peiyong; Sadoshima, Junichi. - In: JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY. - ISSN 1558-3597. - (In corso di stampa).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1096940
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