Long-Term Caloric Restriction Improves Cardiac Function, Remodeling, Adrenergic Responsiveness, and Sympathetic Innervation in a Model of Postischemic Heart Failure

Claudio de Lucia, Giuseppina Gambino, Laura Petraglia, Andrea Elia, Klara Komici, Grazia Daniela Femminella, Maria Loreta D'Amico, Roberto Formisano, Giulia Borghetti, Daniela Liccardo, Maria Nolano, Steven R Houser, Dario Leosco, Nicola Ferrara, Walter J Koch, Giuseppe Rengo

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Caloric restriction (CR) has been described to have cardioprotective effects and improve functional outcomes in animal models and humans. Chronic ischemic heart failure (HF) is associated with reduced cardiac sympathetic innervation, dysfunctional β-adrenergic receptor signaling, and decreased cardiac inotropic reserve. We tested the effects of a long-term CR diet, started late after myocardial infarction on cardiac function, sympathetic innervation, and β-adrenergic receptor responsiveness in a rat model of postischemic HF.

METHODS AND RESULTS: Adult male rats were randomly assigned to myocardial infarction or sham operation and 4 weeks later were further randomized to a 1-year CR or normal diet. One year of CR resulted in a significant reduction in body weight, heart weight, and heart weight/tibia length ratio when compared with normal diet in HF groups. At the end of the study period, echocardiography and histology revealed that HF animals under the CR diet had ameliorated left ventricular remodeling compared with HF rats fed with normal diet. Invasive hemodynamic showed a significant improvement of cardiac inotropic reserve in CR HF rats compared with HF-normal diet animals. Importantly, CR dietary regimen was associated with a significant increase of cardiac sympathetic innervation and with normalized cardiac β-adrenergic receptor levels in HF rats when compared with HF rats on the standard diet.

CONCLUSIONS: We demonstrate, for the first time, that chronic CR, when started after HF established, can ameliorate cardiac dysfunction and improve inotropic reserve. At the molecular level, we find that chronic CR diet significantly improves sympathetic cardiac innervation and β-adrenergic receptor levels in failing myocardium.

Original languageEnglish
Pages (from-to)e004153
JournalCirculation. Heart failure
Volume11
Issue number3
DOIs
Publication statusPublished - Mar 2018

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Caloric Restriction
Adrenergic Agents
Heart Failure
Diet
Adrenergic Receptors
Myocardial Infarction
Weights and Measures
Ventricular Remodeling
Tibia
Echocardiography
Myocardium
Histology
Animal Models
Hemodynamics
Body Weight

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Long-Term Caloric Restriction Improves Cardiac Function, Remodeling, Adrenergic Responsiveness, and Sympathetic Innervation in a Model of Postischemic Heart Failure. / de Lucia, Claudio; Gambino, Giuseppina; Petraglia, Laura; Elia, Andrea; Komici, Klara; Femminella, Grazia Daniela; D'Amico, Maria Loreta; Formisano, Roberto; Borghetti, Giulia; Liccardo, Daniela; Nolano, Maria; Houser, Steven R; Leosco, Dario; Ferrara, Nicola; Koch, Walter J; Rengo, Giuseppe.

In: Circulation. Heart failure, Vol. 11, No. 3, 03.2018, p. e004153.

Research output: Contribution to journalArticle

de Lucia, C, Gambino, G, Petraglia, L, Elia, A, Komici, K, Femminella, GD, D'Amico, ML, Formisano, R, Borghetti, G, Liccardo, D, Nolano, M, Houser, SR, Leosco, D, Ferrara, N, Koch, WJ & Rengo, G 2018, 'Long-Term Caloric Restriction Improves Cardiac Function, Remodeling, Adrenergic Responsiveness, and Sympathetic Innervation in a Model of Postischemic Heart Failure', Circulation. Heart failure, vol. 11, no. 3, pp. e004153. https://doi.org/10.1161/CIRCHEARTFAILURE.117.004153
de Lucia, Claudio ; Gambino, Giuseppina ; Petraglia, Laura ; Elia, Andrea ; Komici, Klara ; Femminella, Grazia Daniela ; D'Amico, Maria Loreta ; Formisano, Roberto ; Borghetti, Giulia ; Liccardo, Daniela ; Nolano, Maria ; Houser, Steven R ; Leosco, Dario ; Ferrara, Nicola ; Koch, Walter J ; Rengo, Giuseppe. / Long-Term Caloric Restriction Improves Cardiac Function, Remodeling, Adrenergic Responsiveness, and Sympathetic Innervation in a Model of Postischemic Heart Failure. In: Circulation. Heart failure. 2018 ; Vol. 11, No. 3. pp. e004153.
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abstract = "BACKGROUND: Caloric restriction (CR) has been described to have cardioprotective effects and improve functional outcomes in animal models and humans. Chronic ischemic heart failure (HF) is associated with reduced cardiac sympathetic innervation, dysfunctional β-adrenergic receptor signaling, and decreased cardiac inotropic reserve. We tested the effects of a long-term CR diet, started late after myocardial infarction on cardiac function, sympathetic innervation, and β-adrenergic receptor responsiveness in a rat model of postischemic HF.METHODS AND RESULTS: Adult male rats were randomly assigned to myocardial infarction or sham operation and 4 weeks later were further randomized to a 1-year CR or normal diet. One year of CR resulted in a significant reduction in body weight, heart weight, and heart weight/tibia length ratio when compared with normal diet in HF groups. At the end of the study period, echocardiography and histology revealed that HF animals under the CR diet had ameliorated left ventricular remodeling compared with HF rats fed with normal diet. Invasive hemodynamic showed a significant improvement of cardiac inotropic reserve in CR HF rats compared with HF-normal diet animals. Importantly, CR dietary regimen was associated with a significant increase of cardiac sympathetic innervation and with normalized cardiac β-adrenergic receptor levels in HF rats when compared with HF rats on the standard diet.CONCLUSIONS: We demonstrate, for the first time, that chronic CR, when started after HF established, can ameliorate cardiac dysfunction and improve inotropic reserve. At the molecular level, we find that chronic CR diet significantly improves sympathetic cardiac innervation and β-adrenergic receptor levels in failing myocardium.",
author = "{de Lucia}, Claudio and Giuseppina Gambino and Laura Petraglia and Andrea Elia and Klara Komici and Femminella, {Grazia Daniela} and D'Amico, {Maria Loreta} and Roberto Formisano and Giulia Borghetti and Daniela Liccardo and Maria Nolano and Houser, {Steven R} and Dario Leosco and Nicola Ferrara and Koch, {Walter J} and Giuseppe Rengo",
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T1 - Long-Term Caloric Restriction Improves Cardiac Function, Remodeling, Adrenergic Responsiveness, and Sympathetic Innervation in a Model of Postischemic Heart Failure

AU - de Lucia, Claudio

AU - Gambino, Giuseppina

AU - Petraglia, Laura

AU - Elia, Andrea

AU - Komici, Klara

AU - Femminella, Grazia Daniela

AU - D'Amico, Maria Loreta

AU - Formisano, Roberto

AU - Borghetti, Giulia

AU - Liccardo, Daniela

AU - Nolano, Maria

AU - Houser, Steven R

AU - Leosco, Dario

AU - Ferrara, Nicola

AU - Koch, Walter J

AU - Rengo, Giuseppe

N1 - © 2018 American Heart Association, Inc.

PY - 2018/3

Y1 - 2018/3

N2 - BACKGROUND: Caloric restriction (CR) has been described to have cardioprotective effects and improve functional outcomes in animal models and humans. Chronic ischemic heart failure (HF) is associated with reduced cardiac sympathetic innervation, dysfunctional β-adrenergic receptor signaling, and decreased cardiac inotropic reserve. We tested the effects of a long-term CR diet, started late after myocardial infarction on cardiac function, sympathetic innervation, and β-adrenergic receptor responsiveness in a rat model of postischemic HF.METHODS AND RESULTS: Adult male rats were randomly assigned to myocardial infarction or sham operation and 4 weeks later were further randomized to a 1-year CR or normal diet. One year of CR resulted in a significant reduction in body weight, heart weight, and heart weight/tibia length ratio when compared with normal diet in HF groups. At the end of the study period, echocardiography and histology revealed that HF animals under the CR diet had ameliorated left ventricular remodeling compared with HF rats fed with normal diet. Invasive hemodynamic showed a significant improvement of cardiac inotropic reserve in CR HF rats compared with HF-normal diet animals. Importantly, CR dietary regimen was associated with a significant increase of cardiac sympathetic innervation and with normalized cardiac β-adrenergic receptor levels in HF rats when compared with HF rats on the standard diet.CONCLUSIONS: We demonstrate, for the first time, that chronic CR, when started after HF established, can ameliorate cardiac dysfunction and improve inotropic reserve. At the molecular level, we find that chronic CR diet significantly improves sympathetic cardiac innervation and β-adrenergic receptor levels in failing myocardium.

AB - BACKGROUND: Caloric restriction (CR) has been described to have cardioprotective effects and improve functional outcomes in animal models and humans. Chronic ischemic heart failure (HF) is associated with reduced cardiac sympathetic innervation, dysfunctional β-adrenergic receptor signaling, and decreased cardiac inotropic reserve. We tested the effects of a long-term CR diet, started late after myocardial infarction on cardiac function, sympathetic innervation, and β-adrenergic receptor responsiveness in a rat model of postischemic HF.METHODS AND RESULTS: Adult male rats were randomly assigned to myocardial infarction or sham operation and 4 weeks later were further randomized to a 1-year CR or normal diet. One year of CR resulted in a significant reduction in body weight, heart weight, and heart weight/tibia length ratio when compared with normal diet in HF groups. At the end of the study period, echocardiography and histology revealed that HF animals under the CR diet had ameliorated left ventricular remodeling compared with HF rats fed with normal diet. Invasive hemodynamic showed a significant improvement of cardiac inotropic reserve in CR HF rats compared with HF-normal diet animals. Importantly, CR dietary regimen was associated with a significant increase of cardiac sympathetic innervation and with normalized cardiac β-adrenergic receptor levels in HF rats when compared with HF rats on the standard diet.CONCLUSIONS: We demonstrate, for the first time, that chronic CR, when started after HF established, can ameliorate cardiac dysfunction and improve inotropic reserve. At the molecular level, we find that chronic CR diet significantly improves sympathetic cardiac innervation and β-adrenergic receptor levels in failing myocardium.

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JO - Circulation: Heart Failure

JF - Circulation: Heart Failure

SN - 1941-3297

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ER -