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Published in: Immunity & Ageing 1/2017

Open Access 01-12-2017 | Research

The anti-ageing molecule sirt1 mediates beneficial effects of cardiac rehabilitation

Authors: Giusy Russomanno, Graziamaria Corbi, Valentina Manzo, Nicola Ferrara, Giuseppe Rengo, Annibale A. Puca, Salvatore Latte, Albino Carrizzo, Maria Consiglia Calabrese, Ramaroson Andriantsitohaina, Walter Filippelli, Carmine Vecchione, Amelia Filippelli, Valeria Conti

Published in: Immunity & Ageing | Issue 1/2017

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Abstract

Background

An exercise-based Cardiac Rehabilitation Programme (CRP) is established as adjuvant therapy in heart failure (HF), nevertheless it is underutilized, especially in the elderly. While the functional and hemodynamic effects of CRP are well known, its underlying molecular mechanisms have not been fully clarified. The present study aims to evaluate the effects of a well-structured 4-week CRP in patients with stable HF from a molecular point of view.

Results

A prospective longitudinal observational study was conducted on patients consecutively admitted to cardiac rehabilitation. In fifty elderly HF patients with preserved ejection fraction (HFpEF), levels of sirtuin 1 (Sirt1) in peripheral blood mononuclear cells (PBMCs) and of its targets, the antioxidants catalase (Cat) and superoxide dismutase (SOD) in serum were measured before (Patients, P) and at the end of the CRP (Rehabilitated Patients, RP), showing a rise of their activities after rehabilitation.
Endothelial cells (ECs) were conditioned with serum from P and RP, and oxidative stress was induced using hydrogen peroxide. An increase of Sirt1 and Cat activity was detected in RP-conditioned ECs in both the absence and presence of oxidative stress, together with a decrease of senescence, an effect not observed during Sirt1 and Cat inhibition.

Conclusions

In addition to the improvement in functional and hemodynamic parameters, a supervised exercise-based CRP increases Sirt1 activity and stimulates a systemic antioxidant defence in elderly HFpEF patients. Moreover, CRP produces antioxidant and anti-senescent effects in human endothelial cells mediated, at least in part, by Sirt1 and its target Cat.
Literature
1.
go back to reference Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation. 2015;131:e29–322.CrossRefPubMed Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation. 2015;131:e29–322.CrossRefPubMed
2.
go back to reference Lawler PR, Filion KB, Eisenberg MJ. Efficacy of exercise-based cardiac rehabilitation post-myocardial infarction: a systematic review and meta-analysis of randomized controlled trials. Am Heart J. 2011;162:571–84. e2.CrossRefPubMed Lawler PR, Filion KB, Eisenberg MJ. Efficacy of exercise-based cardiac rehabilitation post-myocardial infarction: a systematic review and meta-analysis of randomized controlled trials. Am Heart J. 2011;162:571–84. e2.CrossRefPubMed
3.
go back to reference Schutzer KA, Graves BS. Barriers and motivations to exercise in older adults. Prev Med. 2004;39:1056–61.CrossRefPubMed Schutzer KA, Graves BS. Barriers and motivations to exercise in older adults. Prev Med. 2004;39:1056–61.CrossRefPubMed
4.
go back to reference Rengo G, Leosco D, Zincarelli C, Marchese M, Corbi G, Liccardo D, et al. Adrenal GRK2 lowering is an underlying mechanism for the beneficial sympathetic effects of exercise training in heart failure. Am J Physiol Heart Circ Physiol. 2010;298:H2032–2038.CrossRefPubMed Rengo G, Leosco D, Zincarelli C, Marchese M, Corbi G, Liccardo D, et al. Adrenal GRK2 lowering is an underlying mechanism for the beneficial sympathetic effects of exercise training in heart failure. Am J Physiol Heart Circ Physiol. 2010;298:H2032–2038.CrossRefPubMed
5.
go back to reference Leosco D, Rengo G, Iaccarino G, Golino L, Marchese M, Fortunato F, et al. Exercise promotes angiogenesis and improves beta-adrenergic receptor signalling in the post-ischaemic failing rat heart. Cardiovasc Res. 2008;78:385–94.CrossRefPubMed Leosco D, Rengo G, Iaccarino G, Golino L, Marchese M, Fortunato F, et al. Exercise promotes angiogenesis and improves beta-adrenergic receptor signalling in the post-ischaemic failing rat heart. Cardiovasc Res. 2008;78:385–94.CrossRefPubMed
6.
go back to reference Nolte K, Herrmann-Lingen C, Wachter R, Gelbrich G, Düngen H-D, Duvinage A, et al. Effects of exercise training on different quality of life dimensions in heart failure with preserved ejection fraction: the Ex-DHF-P trial. Eur J Prev Cardiol. 2015;22:582–93.CrossRefPubMed Nolte K, Herrmann-Lingen C, Wachter R, Gelbrich G, Düngen H-D, Duvinage A, et al. Effects of exercise training on different quality of life dimensions in heart failure with preserved ejection fraction: the Ex-DHF-P trial. Eur J Prev Cardiol. 2015;22:582–93.CrossRefPubMed
7.
go back to reference Ismail H, McFarlane JR, Nojoumian AH, Dieberg G, Smart NA. Clinical outcomes and cardiovascular responses to different exercise training intensities in patients with heart failure: a systematic review and meta-analysis. JACC Heart Fail. 2013;1:514–22.CrossRefPubMed Ismail H, McFarlane JR, Nojoumian AH, Dieberg G, Smart NA. Clinical outcomes and cardiovascular responses to different exercise training intensities in patients with heart failure: a systematic review and meta-analysis. JACC Heart Fail. 2013;1:514–22.CrossRefPubMed
8.
go back to reference Corbi G, Conti V, Russomanno G, Rengo G, Vitulli P, Ciccarelli AL, et al. Is physical activity able to modify oxidative damage in cardiovascular aging? Oxid Med Cell Longev. 2012;2012:728547.CrossRefPubMedPubMedCentral Corbi G, Conti V, Russomanno G, Rengo G, Vitulli P, Ciccarelli AL, et al. Is physical activity able to modify oxidative damage in cardiovascular aging? Oxid Med Cell Longev. 2012;2012:728547.CrossRefPubMedPubMedCentral
9.
go back to reference Meyer P, Gayda M, Juneau M, Nigam A. High-intensity aerobic interval exercise in chronic heart failure. Curr Heart Fail Rep. 2013;10:130–8.CrossRefPubMed Meyer P, Gayda M, Juneau M, Nigam A. High-intensity aerobic interval exercise in chronic heart failure. Curr Heart Fail Rep. 2013;10:130–8.CrossRefPubMed
11.
go back to reference Corbi G, Conti V, Russomanno G, Longobardi G, Furgi G, Filippelli A, et al. Adrenergic signaling and oxidative stress: a role for sirtuins? Front Physiol. 2013;4:324.CrossRefPubMedPubMedCentral Corbi G, Conti V, Russomanno G, Longobardi G, Furgi G, Filippelli A, et al. Adrenergic signaling and oxidative stress: a role for sirtuins? Front Physiol. 2013;4:324.CrossRefPubMedPubMedCentral
12.
go back to reference Yu W, Fu Y-C, Chen C-J, Wang X, Wang W. SIRT1: a novel target to prevent atherosclerosis. J Cell Biochem. 2009;108:10–3.CrossRefPubMed Yu W, Fu Y-C, Chen C-J, Wang X, Wang W. SIRT1: a novel target to prevent atherosclerosis. J Cell Biochem. 2009;108:10–3.CrossRefPubMed
13.
go back to reference Rahman M, Halade GV, Bhattacharya A, Fernandes G. The fat-1 transgene in mice increases antioxidant potential, reduces pro-inflammatory cytokine levels, and enhances PPAR-gamma and SIRT-1 expression on a calorie restricted diet. Oxid Med Cell Longev. 2009;2:307–16.CrossRefPubMedPubMedCentral Rahman M, Halade GV, Bhattacharya A, Fernandes G. The fat-1 transgene in mice increases antioxidant potential, reduces pro-inflammatory cytokine levels, and enhances PPAR-gamma and SIRT-1 expression on a calorie restricted diet. Oxid Med Cell Longev. 2009;2:307–16.CrossRefPubMedPubMedCentral
14.
go back to reference Conti V, Corbi G, Simeon V, Russomanno G, Manzo V, Ferrara N, et al. Aging-related changes in oxidative stress response of human endothelial cells. Aging Clin Exp Res. 2015;27:547–53.CrossRefPubMed Conti V, Corbi G, Simeon V, Russomanno G, Manzo V, Ferrara N, et al. Aging-related changes in oxidative stress response of human endothelial cells. Aging Clin Exp Res. 2015;27:547–53.CrossRefPubMed
15.
go back to reference Lu T-M, Tsai J-Y, Chen Y-C, Huang C-Y, Hsu H-L, Weng C-F, et al. Downregulation of Sirt1 as aging change in advanced heart failure. J Biomed Sci. 2014;21:57.CrossRefPubMedPubMedCentral Lu T-M, Tsai J-Y, Chen Y-C, Huang C-Y, Hsu H-L, Weng C-F, et al. Downregulation of Sirt1 as aging change in advanced heart failure. J Biomed Sci. 2014;21:57.CrossRefPubMedPubMedCentral
16.
go back to reference Ferrara N, Rinaldi B, Corbi G, Conti V, Stiuso P, Boccuti S, et al. Exercise training promotes SIRT1 activity in aged rats. Rejuvenation Res. 2008;11:139–50.CrossRefPubMed Ferrara N, Rinaldi B, Corbi G, Conti V, Stiuso P, Boccuti S, et al. Exercise training promotes SIRT1 activity in aged rats. Rejuvenation Res. 2008;11:139–50.CrossRefPubMed
17.
go back to reference Leopold JA, Loscalzo J. Oxidative enzymopathies and vascular disease. Arterioscler Thromb Vasc Biol. 2005;25:1332–40.CrossRefPubMed Leopold JA, Loscalzo J. Oxidative enzymopathies and vascular disease. Arterioscler Thromb Vasc Biol. 2005;25:1332–40.CrossRefPubMed
18.
go back to reference Qin F, Lennon-Edwards S, Lancel S, Biolo A, Siwik DA, Pimentel DR, et al. Cardiac-specific overexpression of catalase identifies hydrogen peroxide-dependent and -independent phases of myocardial remodeling and prevents the progression to overt heart failure in G(alpha)q-overexpressing transgenic mice. Circ Heart Fail. 2010;3:306–13.CrossRefPubMed Qin F, Lennon-Edwards S, Lancel S, Biolo A, Siwik DA, Pimentel DR, et al. Cardiac-specific overexpression of catalase identifies hydrogen peroxide-dependent and -independent phases of myocardial remodeling and prevents the progression to overt heart failure in G(alpha)q-overexpressing transgenic mice. Circ Heart Fail. 2010;3:306–13.CrossRefPubMed
19.
go back to reference Conti V, Forte M, Corbi G, Russomanno G, Formisano L, Landolfi A, Izzo V, Filippelli A, Vecchione C, Carrizzo A. Sirtuins: Possible Clinical Implications in Cardio and Cerebrovascular Diseases. Curr Drug Targets. 2017;18(4):473–84. Conti V, Forte M, Corbi G, Russomanno G, Formisano L, Landolfi A, Izzo V, Filippelli A, Vecchione C, Carrizzo A. Sirtuins: Possible Clinical Implications in Cardio and Cerebrovascular Diseases. Curr Drug Targets. 2017;18(4):473–84.
20.
go back to reference Conti V, Corbi G, Russomanno G, Simeon V, Ferrara N, Filippelli W, et al. Oxidative stress effects on endothelial cells treated with different athletes’ sera. Med Sci Sports Exerc. 2012;44:39–49.CrossRefPubMed Conti V, Corbi G, Russomanno G, Simeon V, Ferrara N, Filippelli W, et al. Oxidative stress effects on endothelial cells treated with different athletes’ sera. Med Sci Sports Exerc. 2012;44:39–49.CrossRefPubMed
21.
go back to reference Conti V, Russomanno G, Corbi G, Guerra G, Grasso C, Filippelli W, et al. Aerobic training workload affects human endothelial cells redox homeostasis. Med Sci Sports Exerc. 2013;45:644–53.CrossRefPubMed Conti V, Russomanno G, Corbi G, Guerra G, Grasso C, Filippelli W, et al. Aerobic training workload affects human endothelial cells redox homeostasis. Med Sci Sports Exerc. 2013;45:644–53.CrossRefPubMed
22.
go back to reference Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129–200.CrossRefPubMed Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129–200.CrossRefPubMed
23.
go back to reference Campisi J. Cellular senescence: putting the paradoxes in perspective. Curr Opin Genet Dev. 2011;21:107–12.CrossRefPubMed Campisi J. Cellular senescence: putting the paradoxes in perspective. Curr Opin Genet Dev. 2011;21:107–12.CrossRefPubMed
24.
go back to reference Minamino T, Komuro I. Vascular cell senescence: contribution to atherosclerosis. Circ Res. 2007;100:15–26.CrossRefPubMed Minamino T, Komuro I. Vascular cell senescence: contribution to atherosclerosis. Circ Res. 2007;100:15–26.CrossRefPubMed
25.
go back to reference Ota H, Eto M, Kano MR, Ogawa S, Iijima K, Akishita M, et al. Cilostazol inhibits oxidative stress-induced premature senescence via upregulation of Sirt1 in human endothelial cells. Arterioscler Thromb Vasc Biol. 2008;28:1634–9.CrossRefPubMed Ota H, Eto M, Kano MR, Ogawa S, Iijima K, Akishita M, et al. Cilostazol inhibits oxidative stress-induced premature senescence via upregulation of Sirt1 in human endothelial cells. Arterioscler Thromb Vasc Biol. 2008;28:1634–9.CrossRefPubMed
26.
go back to reference Song Z, Liu Y, Hao B, Yu S, Zhang H, Liu D, et al. Ginsenoside Rb1 prevents H2O2-induced HUVEC senescence by stimulating sirtuin-1 pathway. PLoS One. 2014;9:e112699.CrossRefPubMedPubMedCentral Song Z, Liu Y, Hao B, Yu S, Zhang H, Liu D, et al. Ginsenoside Rb1 prevents H2O2-induced HUVEC senescence by stimulating sirtuin-1 pathway. PLoS One. 2014;9:e112699.CrossRefPubMedPubMedCentral
27.
go back to reference Ota H, Eto M, Kano MR, Kahyo T, Setou M, Ogawa S, et al. Induction of endothelial nitric oxide synthase, SIRT1, and catalase by statins inhibits endothelial senescence through the Akt pathway. Arterioscler Thromb Vasc Biol. 2010;30:2205–11.CrossRefPubMed Ota H, Eto M, Kano MR, Kahyo T, Setou M, Ogawa S, et al. Induction of endothelial nitric oxide synthase, SIRT1, and catalase by statins inhibits endothelial senescence through the Akt pathway. Arterioscler Thromb Vasc Biol. 2010;30:2205–11.CrossRefPubMed
28.
go back to reference Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, et al. Extension of murine life span by overexpression of catalase targeted to mitochondria. Science. 2005;308:1909–11.CrossRefPubMed Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, et al. Extension of murine life span by overexpression of catalase targeted to mitochondria. Science. 2005;308:1909–11.CrossRefPubMed
29.
go back to reference Ge W, Ge W, Zhang Y, Han X, Ren J. Cardiac-specific overexpression of catalase attenuates paraquat-induced myocardial geometric and contractile alteration: role of ER stress. Free Radic Biol Med. 2010;49:2068–77.CrossRefPubMedPubMedCentral Ge W, Ge W, Zhang Y, Han X, Ren J. Cardiac-specific overexpression of catalase attenuates paraquat-induced myocardial geometric and contractile alteration: role of ER stress. Free Radic Biol Med. 2010;49:2068–77.CrossRefPubMedPubMedCentral
30.
go back to reference Massie BM, Carson PE, McMurray JJ, Komajda M, McKelvie R, Zile MR, Anderson S, Donovan M, Iverson E, Staiger C, Ptaszynska A. I-PRESERVE Investigators. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008;359:2456–67.CrossRefPubMed Massie BM, Carson PE, McMurray JJ, Komajda M, McKelvie R, Zile MR, Anderson S, Donovan M, Iverson E, Staiger C, Ptaszynska A. I-PRESERVE Investigators. Irbesartan in patients with heart failure and preserved ejection fraction. N Engl J Med. 2008;359:2456–67.CrossRefPubMed
31.
go back to reference Kitzman DW, Hundley WG, Brubaker PH, Morgan TM, Moore JB, Stewart KP, Little WC. A randomized double-blind trial of enalapril in older patients with heart failure and preserved ejection fraction: effects on exercise tolerance and arterial distensibility. Circ Heart Fail. 2010;3:477–85.CrossRefPubMedPubMedCentral Kitzman DW, Hundley WG, Brubaker PH, Morgan TM, Moore JB, Stewart KP, Little WC. A randomized double-blind trial of enalapril in older patients with heart failure and preserved ejection fraction: effects on exercise tolerance and arterial distensibility. Circ Heart Fail. 2010;3:477–85.CrossRefPubMedPubMedCentral
32.
go back to reference Upadhya B, Haykowsky MJ, Eggebeen J, Kitzman DW. Exercise intolerance in heart failure with preserved ejection fraction: more than a heart problem. J Geriatr Cardiol. 2015;12:294–304.PubMedPubMedCentral Upadhya B, Haykowsky MJ, Eggebeen J, Kitzman DW. Exercise intolerance in heart failure with preserved ejection fraction: more than a heart problem. J Geriatr Cardiol. 2015;12:294–304.PubMedPubMedCentral
33.
go back to reference Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016;18:891–975.CrossRefPubMed Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016;18:891–975.CrossRefPubMed
35.
go back to reference Gallo V, Egger M, McCormack V, Farmer PB, Ioannidis JPA, Kirsch-Volders M, et al. STrengthening the Reporting of OBservational studies in Epidemiology--Molecular Epidemiology (STROBE-ME): an extension of the STROBE Statement. PLoS Med. 2011;8:e1001117.CrossRefPubMedPubMedCentral Gallo V, Egger M, McCormack V, Farmer PB, Ioannidis JPA, Kirsch-Volders M, et al. STrengthening the Reporting of OBservational studies in Epidemiology--Molecular Epidemiology (STROBE-ME): an extension of the STROBE Statement. PLoS Med. 2011;8:e1001117.CrossRefPubMedPubMedCentral
Metadata
Title
The anti-ageing molecule sirt1 mediates beneficial effects of cardiac rehabilitation
Authors
Giusy Russomanno
Graziamaria Corbi
Valentina Manzo
Nicola Ferrara
Giuseppe Rengo
Annibale A. Puca
Salvatore Latte
Albino Carrizzo
Maria Consiglia Calabrese
Ramaroson Andriantsitohaina
Walter Filippelli
Carmine Vecchione
Amelia Filippelli
Valeria Conti
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Immunity & Ageing / Issue 1/2017
Electronic ISSN: 1742-4933
DOI
https://doi.org/10.1186/s12979-017-0088-1

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