运动诱导心脏再生: 治疗心血管疾病的新途径

doi:10.3969/j.issn.1007-2861.2016.03.018

Abstract

Abstract:

Adult mammalian heart has limited regenerative capacity, obviously insufficient to recover cardiomyocyte loss after injury. Exercise can induce cardiac regeneration, not only through promoting cardiomyocyte hypertrophy and renewal while reducing apoptosis, but also through modulating the functions of endothelial cells and fibroblasts. IGF-1/PI3K/Akt signaling, C/EBPβ/CITED4 transcription factors and nitric oxide are essential molecular mechanisms mediating exercise-induced cardiac regeneration. In addition increasing interests are focused on the roles of microRNAs, considered as important biomarkers, in exercise-induced cardiac regeneration. More importantly, exercise-induced cardiac regeneration protects against myocardial infarction, ischemia-reperfusion injury, metabolic cardiomyopathy, and aging-related myocardial injury. Exercise-induced cardiac regeneration may be a potential therapeutic strategy for cardiovascular diseases.

Key words: cardiomyocyte , exercise , stem cell, cardiac regeneration

BEI Yihua, XIAO Junjie. Exercise-induced cardiac regeneration: new therapeutic strategy for cardiovascular diseases[J]. Journal of Shanghai University（Natural Science Edition）, 2016, 22(3): 293-301.

References

[1] White H D, Chew D P. Acute myocardial infarction [J]. Lancet, 2008, 372(9638): 570-584.
[2] Roger V L, Go A S, Lloyd-Jones D M, et al. Heart disease and stroke statistics—2012 update: a report from the American Heart Association [J]. Circulation, 2012, 125(1): e2-e220.
[3] Narula J, Haider N, Virmani R, et al. Apoptosis in myocytes in end-stage heart failure [J]. New England Journal of Medicine, 1996, 335(16): 1182-1189.
[4] Ali S R, Hippenmeyer S, Saadat L V, et al. Existing cardiomyocytes generate cardiomyocytes at a low rate after birth in mice [J]. Proceedings of the National Academy of Sciences of the United States of America, 2014, 111(24): 8850-8855.

[5] Beltrami A P, Barlucchi L, Torella D, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration [J]. Cell, 2003, 114(6): 763-776.
[6] Bersell K, Arab S, Haring B, et al. Neuregulin1/ErbB4 signaling induces cardiomyocyte proliferation and repair of heart injury [J]. Cell, 2009, 138(2): 257-270.
[7] Kikuchi K, Holdway J E, Werdich A A, et al. Primary contribution to zebrafish heart regeneration by gata4(+) cardiomyocytes [J]. Nature, 2010, 464(7288): 601-605.
[8] Hsieh P C, Segers V F, Davis M E, et al. Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury [J]. Nature Medicine, 2007,
13(8): 970-974.
[9] Tao L, Bei Y, Zhang H, et al. Exercise for the heart: signaling pathways [J]. Oncotarget, 2015, 6(25): 20773-20784.
[10] Ellison G M, Waring C D, Vicinanza C, et al. Physiological cardiac remodelling in response to endurance exercise training: cellular and molecular mechanisms [J]. Heart, 2012, 98(1): 5-10.
[11] Lerchenmuller C, Rosenzweig A. Mechanisms of exercise-induced cardiac growth [J]. Drug Discovery Today, 2014, 19(7): 1003-1009.
[12] Takefuji M, Wirth A, Lukasova M, et al. G(13)-mediated signaling pathway is required for pressure overload-induced cardiac remodeling and heart failure [J]. Circulation, 2012, 126(16): 1972-1982.
[13] Komajda M, Lam C S. Heart failure with preserved ejection fraction: a clinical dilemma [J]. European Heart Journal, 2014, 35(16): 1022-1032.
[14] Burchfield J S, Xie M, Hill J A. Pathological ventricular remodeling: mechanisms: part 1 of 2 [J]. Circulation, 2013, 128(4): 388-400.
[15] Anderson L, Oldridge N, Thompson D R, et al. Exercise-based cardiac rehabilitation for coronary heart disease: cochrane systematic review and Meta-analysis [J]. Journal of the American College of Cardiology, 2016, 67(1): 1-12.
[16] Weiner R B, Baggish A L. Exercise-induced cardiac remodeling [J]. Progress in Cardiovascular Diseases, 2012, 54(5): 380-386.
[17] Kemi O J, Loennechen J P, Wisloff U, et al. Intensity-controlled treadmill running in mice: cardiac and skeletal muscle hypertrophy [J]. Journal of Applied Physiology (1985), 2002, 93(4): 1301-1309.
[18] Bergmann O, Bhardwaj R D, Bernard S, et al. Evidence for cardiomyocyte renewal in humans [J]. Science, 2009, 324(5923): 98-102.
[19] Bostrom P, Mann N, Wu J, et al. C/EBPbeta controls exercise-induced cardiac growth and protects against pathological cardiac remodeling [J]. Cell, 2010, 143(7): 1072-1083.
[20] Liu X, Xiao J, Zhu H, et al. miR-222 is necessary for exercise-induced cardiac growth and protects against pathological cardiac remodeling [J]. Cell Metabolism, 2015, 21(4): 584-595.
[21] Figueiredo P A, Appell C H J, Duarte J A. Cardiac regeneration and cellular therapy: is there a benefit of exercise? [J]. International Journal of Sports Medicine, 2014, 35(3): 181-190.
[22] Leri A, Kajstura J, Anversa P. Cardiac stem cells and mechanisms of myocardial regeneration[J]. Physiological Reviews, 2005, 85(4): 1373-1416.

[23] Henning R J. Stem cells in cardiac repair [J]. Future Cardiology, 2011, 7(1): 99-117.
[24] Kolwicz S C, Macdonnell S M, Renna B F, et al. Left ventricular remodeling with exercise in hypertension [J]. American Journal of Physiology: Heart and Circulatory Physiology, 2009, 297(4): H1361-H1368.
[25] Xiao J, Xu T, Li J, et al. Exercise-induced physiological hypertrophy initiates activation of cardiac progenitor cells [J]. International Journal of Clinical and Experimental Pathology, 2014, 7(2): 663-669.
[26] Tao L, Bei Y, Lin S, et al. Exercise training protects against acute myocardial infarction via improving myocardial energy metabolism and mitochondrial biogenesis [J]. Cellular Physiology and Biochemistry, 2015, 37(1): 162-175.
[27] Wang H, Bei Y, Lu Y, et al. Exercise prevents cardiac injury and improves mitochondrial biogenesis in advanced diabetic cardiomyopathy with PGC-1alpha and Akt activation [J]. Cellular Physiology and Biochemistry, 2015, 35(6): 2159-2168.
[28] Kim J, Wende A R, Sena S, et al. Insulin-like growth factor Ⅰreceptor signaling is required for exercise-induced cardiac hypertrophy [J]. Molecular Endocrinology, 2008, 22(11): 2531-2543.
[29] Delaughter M C, Taffet G E, Fiorotto M L, et al. Local insulin-like growth factorⅠexpression induces physiologic, then pathologic, cardiac hypertrophy in transgenic mice [J].
FASEB Journal, 1999, 13(14): 1923-1929.
[30] Luo J, Mcmullen J R, Sobkiw C L, et al. Class IA phosphoinositide 3-kinase regulates heart size and physiological cardiac hypertrophy [J]. Molecular and Cellular Biology, 2005, 25(21): 9491-9502.
[31] Debosch B, Treskov I, Lupu T S, et al. Akt1 is required for physiological cardiac growth [J]. Circulation, 2006, 113(17): 2097-2104.
[32] Sebastian T, Johnson P F. Stop and go: anti-proliferative and mitogenic functions of the transcription factor C/EBPbeta [J]. Cell Cycle, 2006, 5(9): 953-957.
[33] Zou J, Li H, Chen X, et al. C/EBPbeta knockdown protects cardiomyocytes from hypertrophy via inhibition of p65-NFkappaB [J]. Molecular and Cellular Endocrinology, 2014, 390(1/2): 18-25.
[34] Akita Y, Otani H, Matsuhisa S, et al. Exercise-induced activation of cardiac sympathetic nerve triggers cardioprotection via redox-sensitive activation of eNOS and upregulation of
iNOS [J]. American Journal of Physiology: Heart and Circulatory Physiology, 2007, 292(5): H2051-H2059.
[35] White F C, Bloor C M, Mckirnan M D, et al. Exercise training in swine promotes growth of arteriolar bed and capillary angiogenesis in heart [J]. Journal of Applied Physiology (1985),
1998, 85(3): 1160-1168.
[36] Kozakova M, Paterni M, Bartolomucci F, et al. Epicardial coronary artery size in hypertensive and physiologic left ventricular hypertrophy [J]. American Journal of Hypertension,
2007, 20(3): 279-284.
[37] Dimmeler S, Fleming I, Fisslthaler B, et al. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation [J]. Nature, 1999, 399(6736): 601-605.

[38] Ribeiro F, Ribeiro I P, Alves A J, et al. Effects of exercise training on endothelial progenitor cells in cardiovascular disease: a systematic review [J]. American Journal of Physical Medicine and Rehabilitation, 2013, 92(11): 1020-1030.
[39] Thijssen D H, Torella D, Hopman M T, et al. The role of endothelial progenitor and cardiac stem cells in the cardiovascular adaptations to age and exercise [J]. Frontiersin Bioscience-Landmark, 2009, 14: 4685-4702.
[40] Calvert J W, Condit M E, Aragon J P, et al. Exercise protects against myocardial ischemiareperfusion injury via stimulation of beta(3)-adrenergic receptors and increased nitric oxide signaling: role of nitrite and nitrosothiols [J]. Circulation Research, 2011, 108(12): 1448-1458.
[41] Calvert J W, Lefer D J. Role of beta-adrenergic receptors and nitric oxide signaling in exercise-mediated cardioprotection [J]. Physiology (Bethesda, Md.), 2013, 28(4): 216-224.
[42] Van Rooij E. The art of microRNA research [J]. Circulation Research, 2011, 108(2): 219-234.
[43] Farh K K, Grimson A, Jan C, et al. The widespread impact of mammalian microRNAs on mRNA repression and evolution [J]. Science, 2005, 310(5755): 1817-1821.
[44] Vegter E L, Van Der Meer P, De Windt L J, et al. MicroRNAs in heart failure: from biomarker to target for therapy [J]. European Journal of Heart Failure, 2016, 18(5): 457-468.
[45] Philippen L E, Dirkx E, Da Costa-Martins P A, et al. Non-coding RNA in control of gene regulatory programs in cardiac development and disease [J]. Journal of Molecular and Cellular Cardiology, 2015, 89(PtA): 51-58.
[46] Care A, Catalucci D, Felicetti F, et al. MicroRNA-133 controls cardiac hypertrophy [J]. Nature Medicine, 2007, 13(5): 613-618.
[47] Lin R C, Weeks K L, Gao X M, et al. PI3K(p110 alpha) protects against myocardial infarctioninduced heart failure: identification of PI3K-regulated miRNA and mRNA [J]. Arteriosclerosis, Thrombosis, and Vascular Biology, 2010, 30(4): 724-732.
[48] Melo S F, Barauna V G, Junior M A, et al. Resistance training regulates cardiac function through modulation of miRNA-214 [J]. International Journal of Molecular Sciences, 2015, 16(4): 6855-6867.
[49] Soci U P, Fernandes T, Hashimoto N Y, et al. MicroRNAs 29 are involved in the improvement of ventricular compliance promoted by aerobic exercise training in rats [J]. Physiological Genomics, 2011, 43(11): 665-673.
[50] Van Rooij E, Sutherland L B, Thatcher J E, et al. Dysregulation of microRNAs after myocardial infarction reveals a role of miR-29 in cardiac fibrosis [J]. Proceedings of the National
Academy of Sciences of the United States of America, 2008, 105(35): 13027-13032.
[51] Xu J, Zhao J, Evan G, et al. Circulating microRNAs: novel biomarkers for cardiovascular diseases [J]. Journal of Molecular Medicine, 2012, 90(8): 865-875.
[52] Melman Y F, Shah R, Danielson K, et al. Circulating microRNA-30d is associated with response to cardiac resynchronization therapy in heart failure and regulates cardiomyocyte apoptosis: a translational pilot study [J]. Circulation, 2015, 131(25): 2202-2216.
[53] Baggish A L, Hale A, Weiner R B, et al. Dynamic regulation of circulating microRNA during acute exhaustive exercise and sustained aerobic exercise training [J]. Journal of Physiology, 2011, 589(Pt16): 3983-3994.

[54] Xu T, Zhou Q, Che L, et al. Circulating miR-21, miR-378, and miR-940 increase in response to an acute exhaustive exercise in chronic heart failure patients [J]. Oncotarget, 2016, 7(11): 12414-12425.
[55] Bei Y, Zhou Q, Sun Q, et al. Exercise as a platform for pharmacotherapy development in cardiac diseases [J]. Curr Pharm Des, 2015, 21(30): 4409-4416.
[56] Tian X F, Cui M X, Yang S W, et al. Cell death, dysglycemia and myocardial infarction [J]. Biomedical Reports, 2013, 1(3): 341-346.
[57] Rodrigues B, Lira F S, Consolim-Colombo F M, et al. Role of exercise training on autonomic changes and inflammatory profile induced by myocardial infarction [J]. Mediators
of Inflammation, 2014, 2014: 702473.
[58] Goldhammer E, Tanchilevitch A, Maor I, et al. Exercise training modulates cytokines activity in coronary heart disease patients [J]. International Journal of Cardiology, 2005, 100(1): 93-99.
[59] Task Force On The Management of Stseamiotesoc, Steg P G, James S K, et al. ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation [J]. European Heart Journal, 2012, 33(20): 2569-2619.
[60] Murphy E, Steenbergen C. Mechanisms underlying acute protection from cardiac ischemiareperfusion injury [J]. Physiological Reviews, 2008, 88(2): 581-609.
[61] Gomes E C, Silva A N, De Oliveira M R. Oxidants, antioxidants, and the beneficial roles of exercise-induced production of reactive species [J]. Oxidative Medicine and Cellular Longevity, 2012, 2012: 756132.
[62] Li J, Zhang H, Zhang C. Role of inflammation in the regulation of coronary blood flow in ischemia and reperfusion: mechanisms and therapeutic implications [J]. Journal of Molecular and Cellular Cardiology, 2012, 52(4): 865-872.
[63] Lopez-Neblina F, Toledo A H, Toledo-Pereyra L H. Molecular biology of apoptosis in ischemia and reperfusion [J]. Journal of Investigative Surgery, 2005, 18(6): 335-350.
[64] Zhang K R, Liu H T, Zhang H F, et al. Long-term aerobic exercise protects the heart against ischemia/reperfusion injury via PI3 kinase-dependent and Akt-mediated mechanism [J]. Apoptosis, 2007, 12(9): 1579-1588.
[65] Kwak H B, Kim J H, Joshi K, et al. Exercise training reduces fibrosis and matrix metalloproteinase dysregulation in the aging rat heart [J]. FASEB Journal, 2011, 25(3): 1106-1117.
[66] Kwak H B. Effects of aging and exercise training on apoptosis in the heart [J]. Journal of Exercise Rehabilitation, 2013, 9(2): 212-219.

Exercise-induced cardiac regeneration: new therapeutic strategy for cardiovascular diseases

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