Exercise and the aging endothelium

Saeid Golbidi, Ismail Laher, Saeid Golbidi, Ismail Laher

Abstract

The endothelium plays a critical role in the maintenance of cardiovascular health by producing nitric oxide and other vasoactive materials. Aging is associated with a gradual decline in this functional aspect of endothelial regulation of cardiovascular homeostasis. Indeed, age is an independent risk factor for cardiovascular diseases and is in part an important factor in the increased exponential mortality rates from vascular disease such as myocardial infarction and stroke that occurs in the ageing population. There are a number of mechanisms suggested to explain age-related endothelial dysfunction. However, recent scientific studies have advanced the notion of oxidative stress and inflammation as the two major risk factors underlying aging and age-related diseases. Regular physical activity, known to have a favorable effect on cardiovascular health, can also improve the function of the ageing endothelium by modulating oxidative stress and inflammatory processes, as we discuss in this paper.

References

    1. Yusuf S, Reddy S, Ôunpuu S, Anand S. Global burden of cardiovascular diseases—part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization. Circulation. 2001;104(22):2746–2753.
    1. National Centre for Health Statistics (US) .
    1. Yu BP. Aging and oxidative stress: modulation by dietary restriction. Free Radical Biology and Medicine. 1996;21(5):651–668.
    1. Beckman KB, Ames BN. The free radical theory of aging matures. Physiological Reviews. 1998;78(2):547–581.
    1. Vita JA. Nitric oxide-dependent vasodilation in human subjects. Methods in Enzymology. 2002;359:186–200.
    1. Bonetti PO, Lerman LO, Lerman A. Endothelial dysfunction: a marker of atherosclerotic risk. Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23(2):168–175.
    1. Anderson TJ. Assessment and treatment of endothelial dysfunction in humans. Journal of the American College of Cardiology. 1999;34(3):631–638.
    1. Chung HY, Kim HJ, Kim JW, Yu BP. The inflammation hypothesis of aging: molecular modulation by calorie restriction. Annals of the New York Academy of Sciences. 2001;928:327–335.
    1. Clarkson P, Montgomery HE, Mullen MJ, et al. Exercise training enhances endothelial function in young men. Journal of the American College of Cardiology. 1999;33(5):1379–1385.
    1. Benjamin EJ, Larson MG, Keyes MJ, et al. Clinical correlates and heritability of flow-mediated dilation in the community: the Framingham Heart Study. Circulation. 2004;109(5):613–619.
    1. Hambrecht R, Fiehn E, Weigl C, et al. Regular physical exercise corrects endothelial dysfunction and improves exercise capacity in patients with chronic heart failure. Circulation. 1998;98(24):2709–2715.
    1. Maiorana A, O’Driscoll G, Cheetham C, et al. The effect of combined aerobic and resistance exercise training on vascular function in type 2 diabetes. Journal of the American College of Cardiology. 2001;38(3):860–866.
    1. Maiorana A, O’Driscoll G, Dembo L, Goodman C, Taylor R, Green D. Exercise training, vascular function, and functional capacity in middle-aged subjects. Medicine and Science in Sports and Exercise. 2001;33(12):2022–2028.
    1. Verma S, Anderson TJ. Fundamentals of endothelial function for the clinical cardiologist. Circulation. 2002;105(5):546–549.
    1. Cosentino F, Osto E. Aging and endothelial dysfunction. Clinical Hemorheology and Microcirculation. 2007;37:143–147.
    1. Deanfield J, Donald A, Ferri C, et al. Endothelial function and dysfunction—part I: methodological issues for assessment in the different vascular beds: a statement by the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension. Journal of Hypertension. 2005;23(1):7–17.
    1. Golbidi S, Mesdaghinia A, Laher I. Exercise in the metabolic syndrome. Oxidative Medicine and Cellular Longevity. 2012;2012:13 pages.349710
    1. Michel JB, Feron O, Sacks D, Michel T. Reciprocal regulation of endothelial nitric-oxide synthase by Ca2+-calmodulin and caveolin. Journal of Biological Chemistry. 1997;272(25):15583–15586.
    1. Dessy C, Feron O, Balligand J-L. The regulation of endothelial nitric oxide synthase by caveolin: a paradigm validated in vivo and shared by the ‘endothelium-derived hyperpolarizing factor’. Pflugers Archiv—European Journal of Physiology. 2010;459(6):817–827.
    1. Bobeuf F, Labonte M, Dionne IJ, Khalil A. Combined effect of antioxidant supplementation and resistance training on oxidative stress markers, muscle and body composition in an elderly population. Journal of Nutrition, Health and Aging. 2011;15(10):883–889.
    1. Anton SD, Manini TM, Milsom VA, et al. Effects of a weight loss plus exercise program on physical function in overweight, older women: a randomized controlled trial. Clinical Interventions in Aging. 2011;6(1):141–149.
    1. Gano LB, Donato AJ, Pierce GL, et al. Increased proinflammatory and oxidant gene expression in circulating mononuclear cells in older adults: amelioration by habitual exercise. Physiological Genomics. 2011;43(14):895–902.
    1. Campbell PT, Gross MD, Potter JD, et al. Effect of exercise on oxidative stress: a 12-month randomized, controlled trial. Medicine and Science in Sports and Exercise. 2010;42(8):1448–1453.
    1. Wray DW, Uberoi A, Lawrenson L, Bailey DM, Richardson RS. Oral antioxidants and cardiovascular health in the exercise-trained and untrained elderly: a radically different outcome. Clinical Science. 2009;116(5):433–441.
    1. Sixt S, Rastan A, Desch S, et al. Exercise training but not rosiglitazone improves endothelial function in prediabetic patients with coronary disease. European Journal of Cardiovascular Prevention and Rehabilitation. 2008;15(4):473–478.
    1. Gonzales JU, Thistlethwaite JR, Thompson BC, Scheuermann BW. Exercise-induced shear stress is associated with changes in plasma von Willebrand factor in older humans. European Journal of Applied Physiology. 2009;106(5):779–784.
    1. Xia W-H, Li J, Su C, et al. Physical exercise attenuates age-associated reduction in endothelium-reparative capacity of endothelial progenitor cells by increasing CXCR4/JAK-2 signaling in healthy men. Aging Cell. 2012;11(1):111–119.
    1. Pierce GL, Eskurza I, Walker AE, Fay TN, Seals DR. Sex-specific effects of habitual aerobic exercise on brachial artery flow-mediated dilation in middle-aged and older adults. Clinical Science. 2011;120(1):13–23.
    1. van Guilder GP, Westby CM, Greiner JJ, Stauffer BL, DeSouza CA. Endothelin-1 vasoconstrictor tone increases with age in healthy men but can be reduced by regular aerobic exercise. Hypertension. 2007;50(2):403–409.
    1. da Silva CA, Ribeiro JP, Canto JCAU, et al. High-intensity aerobic training improves endothelium-dependent vasodilation in patients with metabolic syndrome and type 2 diabetes mellitus. Diabetes Research and Clinical Practice. 2012;95(2):237–245.
    1. Okada S, Hiuge A, Makino H, et al. Effect of exercise intervention on endothelial function and incidence of cardiovascular disease in patients with type 2 diabetes. Journal of Atherosclerosis and Thrombosis. 2010;17(8):828–833.
    1. Vona M, Codeluppi GM, Iannino T, Ferrari E, Bogousslavsky J, von Segesser LK. Effects of different types of exercise training followed by detraining on endothelium-dependent dilation in patients with recent myocardial infarction. Circulation. 2009;119(12):1601–1608.
    1. Yamamoto K, Ando J. New molecular mechanisms for cardiovascular disease: blood flow sensing mechanism in vascular endothelial cells. Journal of Pharmacological Sciences. 2011;116(4):323–331.
    1. Gielen S, Schuler G, Adams V. Cardiovascular effects of exercise training: molecular mechanisms. Circulation. 2010;122(12):1221–1238.
    1. Stuart CA, Shangraw RE, Prince MJ, Peters EJ, Wolfe RR. Bed-rest-induced insulin resistance occurs primarily in muscle. Metabolism. 1988;37(8):802–806.
    1. Arciero PJ, Smith DL, Calles-Escandon J. Effects of short-term inactivity on glucose tolerance, energy expenditure, and blood flow in trained subjects. Journal of Applied Physiology. 1998;84(4):1365–1373.
    1. Smorawiński J, Kaciuba-Uściłko H, Nazar K, et al. Effects of three-day bed rest on metabolic, hormonal and circulatory responses to an oral glucose load in endurance or strength trained athletes and untrained subjects. Journal of Physiology and Pharmacology. 2000;51(2):279–289.
    1. Thosar SS, Johnson BD, Johnston JD, Wallace JP. Sitting and endothelial dysfunction: the role of shear stress. Medical Science Monitor. 2012;18:RA173–RA180.
    1. Demiot C, Dignat-George F, Fortrat J-O, et al. WISE 2005: chronic bed rest impairs microcirculatory endothelium in women. American Journal of Physiology—Heart and Circulatory Physiology. 2007;293(5):H3159–H3164.
    1. di Francescomarino S, Sciartilli A, di Valerio V, di Baldassarre A, Gallina S. The effect of physical exercise on endothelial function. Sports Medicine. 2009;39(10):797–812.
    1. Luscher TF, Noll G. The endothelium in coronary vascular control. Heart Disease. 1995;3:1–10.
    1. Vanhoutte PW. Ageing and endothelial dysfunction. European Heart Journal. 2002;4:A8–A17.
    1. Lakatta EG. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises—part III: cellular and molecular clues to heart and arterial aging. Circulation. 2003;107(3):490–497.
    1. Brandes RP, Fleming I, Busse R. Endothelial aging. Cardiovascular Research. 2005;66(2):286–294.
    1. Rahman K. Studies on free radicals, antioxidants, and co-factors. Clinical Interventions in Aging. 2007;2(2):219–236.
    1. Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circulation Research. 2000;87(10):840–844.
    1. Taddei S, Virdis A, Ghiadoni L, et al. Age-related reduction of NO availability and oxidative stress in humans. Hypertension. 2001;38(2):274–279.
    1. Sun D, Huang A, Yan EH, et al. Reduced release of nitric oxide to shear stress in mesenteric arteries of aged rats. American Journal of Physiology—Heart and Circulatory Physiology. 2004;286(6):H2249–H2256.
    1. Minamino T, Miyauchi H, Yoshida T, Ishida Y, Yoshida H, Komuro I. Endothelial cell senescence in human atherosclerosis: role of telomere in endothelial dysfunction. Circulation. 2002;105(13):1541–1544.
    1. Durrant JR, Seals DR, Connell ML, et al. Voluntary wheel running restores endothelial function in conduit arteries of old mice: direct evidence for reduced oxidative stress, increased superoxide dismutase activity and down-regulation of NADPH oxidase. Journal of Physiology. 2009;587(13):3271–3285.
    1. van der Loo B, Labugger R, Skepper JN, et al. Enhanced peroxynitrite formation is associated with vascular aging. Journal of Experimental Medicine. 2000;192(12):1731–1743.
    1. Cernadas MR, Sánchez de Miguel L, García-Durán M, et al. Expression of constitutive and inducible nitric oxide synthases in the vascular wall of young and aging rats. Circulation Research. 1998;83(3):279–286.
    1. Pennathur S, Heinecke JW. Oxidative stress and endothelial dysfunction in vascular disease. Current Diabetes Reports. 2007;7(4):257–264.
    1. Versari D, Daghini E, Virdis A, Ghiadoni L, Taddei S. The ageing endothelium, cardiovascular risk and disease in man. Experimental Physiology. 2009;94(3):317–321.
    1. Hamilton CA, Brosnan MJ, McIntyre M, Graham D, Dominiczak AF. Superoxide excess in hypertension and aging a common cause of endothelial dysfunction. Hypertension. 2001;37(2):529–534.
    1. Görlach A, Brandes RP, Nguyen K, Amidi M, Dehghani F, Busse R. A gp91phox containing NADPH oxidase selectively expressed in endothelial cells is a major source of oxygen radical generation in the arterial wall. Circulation Research. 2000;87(1):26–32.
    1. Jung O, Schreiber JG, Geiger H, Pedrazzini T, Busse R, Brandes RP. gp91phox-containing NADPH oxidase mediates endothelial dysfunction in renovascular hypertension. Circulation. 2004;109(14):1795–1801.
    1. Donato AJ, Eskurza I, Silver AE, et al. Direct evidence of endothelial oxidative stress with aging in humans: relation to impaired endothelium-dependent dilation and upregulation of nuclear factor-κB. Circulation Research. 2007;100(11):1659–1666.
    1. Turko IV, Marcondes S, Murad F. Diabetes-associated nitration of tyrosine and inactivation of succinyl-CoA:3-oxoacid CoA-transferase. American Journal of Physiology—Heart and Circulatory Physiology. 2001;281(6):H2289–H2294.
    1. Liu Y, Gutterman DD. The coronary circulation in diabetes: influence of reactive oxygen species on K+ channel-mediated vasodilation. Vascular Pharmacology. 2002;38(1):43–49.
    1. Liu Y, Terata K, Chai Q, Li H, Kleinman LH, Gutterman DD. Peroxynitrite inhibits Ca2+-activated K+ channel activity in smooth muscle of human coronary arterioles. Circulation Research. 2002;91(11):1070–1076.
    1. Soriano F, Virág L, Szabó C. Diabetic endothelial dysfunction: role of reactive oxygen and nitrogen species production and poly(ADP-ribose) polymerase activation. Journal of Molecular Medicine. 2001;79(8):437–448.
    1. Eskurza I, Myerburgh LA, Kahn ZD, Seals DR. Tetrahydrobiopterin augments endothelium-dependent dilatation in sedentary but not in habitually exercising older adults. Journal of Physiology. 2005;568(3):1057–1065.
    1. Lee S, Park Y, Zuidema MY, Hannink M, Zhang C. Effects of interventions on oxidative stress and inflammation of cardiovascular diseases. World Journal of Cardiology. 2011;3:18–24.
    1. Barton M, Cosentino F, Brandes RP, Moreau P, Shaw S, Lüscher TF. Anatomic heterogeneity of vascular aging: role of nitric oxide and endothelin. Hypertension. 1997;30(4):817–824.
    1. He T, Joyner MJ, Katusic ZS. Aging decreases expression and activity of glutathione peroxidase-1 in human endothelial progenitor cells. Microvascular Research. 2009;78(3):447–452.
    1. Leung FP, Yung LM, Laher I, Yao X, Chen ZY, Huang Y. Exercise, vascular wall and cardiovascular diseases: an update (part 1) Sports Medicine. 2008;38(12):1009–1024.
    1. Balducci S, Zanuso S, Nicolucci A, et al. Anti-inflammatory effect of exercise training in subjects with type 2 diabetes and the metabolic syndrome is dependent on exercise modalities and independent of weight loss. Nutrition, Metabolism and Cardiovascular Diseases. 2010;20(8):608–617.
    1. Sprague AH, Khalil RA. Inflammatory cytokines in vascular dysfunction and vascular disease. Biochemical Pharmacology. 2009;78(6):539–552.
    1. Tiwari S, Zhang Y, Heller J, Abernethy DR, Soldatov NM. Artherosclerosis-related molecular alteration of the human Ca V1.2 calcium channel α1C subunit. Proceedings of the National Academy of Sciences of the United States of America. 2006;103(45):17024–17029.
    1. Hiroki J, Shimokawa H, Higashi M, et al. Inflammatory stimuli upregulate Rho-kinase in human coronary vascular smooth muscle cells. Journal of Molecular and Cellular Cardiology. 2004;37(2):537–546.
    1. Zhang C, Park Y, Picchi A, Potter BJ. Maturation-induces endothelial dysfunction via vascular inflammation in diabetic mice. Basic Research in Cardiology. 2008;103(5):407–416.
    1. Mitchell JA, Larkin S, Williams TJ. Cyclooxygenase-2: regulation and relevance in inflammation. Biochemical Pharmacology. 1995;50(10):1535–1542.
    1. Erdei N, Bagi Z, Édes I, Kaley G, Koller A. H2O2 increases production of constrictor prostaglandins in smooth muscle leading to enhanced arteriolar tone in type 2 diabetic mice. American Journal of Physiology—Heart and Circulatory Physiology. 2007;292(1):H649–H656.
    1. Matsumoto T, Kakami M, Noguchi E, Kobayashi T, Kamata K. Imbalance between endothelium-derived relaxing and contracting factors in mesenteric arteries from aged OLETF rats, a model of type 2 diabetes. American Journal of Physiology—Heart and Circulatory Physiology. 2007;293(3):H1480–H1490.
    1. Tang EHC, Leung FP, Huang Y, et al. Calcium and reactive oxygen species increase in endothelial cells in response to releasers of endothelium-derived contracting factor. British Journal of Pharmacology. 2007;151(1):15–23.
    1. Kim HJ, Jung KJ, Yu BP, Cho CG, Choi JS, Chung HY. Modulation of redox-sensitive transcription factors by calorie restriction during aging. Mechanisms of Ageing and Development. 2002;123(12):1589–1595.
    1. Chung HY, Sung B, Jung KJ, Zou Y, Yu BP. The molecular inflammatory process in aging. Antioxidants and Redox Signaling. 2006;8(3-4):572–581.
    1. Baldwin AS., Jr. The NF-kappa B and I kappa B proteins: new discoveries and insights. The Annual Review of Immunology. 1996;14:649–683.
    1. Barnes PJ, Karin M. Nuclear factor-κB—a pivotal transcription factor in chronic inflammatory diseases. The New England Journal of Medicine. 1997;336(15):1066–1071.
    1. Ghosh S, May MJ, Kopp EB. NF-κB and rel proteins: evolutionarily conserved mediators of immune responses. Annual Review of Immunology. 1998;16:225–260.
    1. Kim HJ, Kim KW, Yu BP, Chung HY. The effect of age on cyclooxygenase-2 gene expression: NF-kappaB activation and IkappaBalpha degradation. Free Radical Biology and Medicine. 2000;28:683–692.
    1. Chung HY, Cesari M, Anton S, et al. Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Research Reviews. 2009;8(1):18–30.
    1. Kritchevsky SB, Cesari M, Pahor M. Inflammatory markers and cardiovascular health in older adults. Cardiovascular Research. 2005;66(2):265–275.
    1. Cartier A, Côté M, Lemieux I, et al. Age-related differences in inflammatory markers in men: contribution of visceral adiposity. Metabolism. 2009;58(10):1452–1458.
    1. Bruunsgaard H, Andersen-Ranberg K, Jeune B, Pedersen AN, Skinhøj P, Pedersen BK. A high plasma concentration of TNF-alpha is associated with dementia in centenarians. The Journal of Gerontology: Series A. 1999;54(7):M357–M364.
    1. Willette AA, Bendlin BB, McLaren DG, et al. Age-related changes in neural volume and microstructure associated with interleukin-6 are ameliorated by a calorie-restricted diet in old rhesus monkeys. NeuroImage. 2010;51(3):987–994.
    1. Devaux B, Scholz D, Hirche A, Klovekorn WP, Schaper J. Upregulation of cell adhesion molecules and the presence of low grade inflammation in human chronic heart failure. European Heart Journal. 1997;18(3):470–479.
    1. Maggio M, Guralnik JM, Longo DL, Ferrucci L. Interleukin-6 in aging and chronic disease: a magnificent pathway. Journals of Gerontology: Series A. 2006;61(6):575–584.
    1. Wannamethee SG, Shaper AG, Whincup PH. Modifiable lifestyle factors and the metabolic syndrome in older men: effects of lifestyle changes. Journal of the American Geriatrics Society. 2006;54(12):1909–1914.
    1. Mokdad AH, Marks JS, Stroup DF, Gerberding JL. Actual causes of death in the United States, 2000. Journal of the American Medical Association. 2004;291(10):1238–1245.
    1. Golbidi S, Laher I. Molecular mechanisms in exercise-induced cardioprotection. Cardiology Research and Practice. 2011;2011:15 pages.972807
    1. Ghosh S, Golbidi S, Werner I, Verchere BC, Laher I. Selecting exercise regimens and strains to modify obesity and diabetes in rodents: an overview. Clinical Science. 2010;119(2):57–74.
    1. Macera CA, Hootman JM, Sniezek JE. Major public health benefits of physical activity. Arthritis Care and Research. 2003;49(1):122–128.
    1. Macera CA, Powell KE. Population attributable risk: implications of physical activity dose. Medicine and Science in Sports and Exercise. 2001;33(6):S635–S639.
    1. Myers J, Kaykha A, George S, et al. Fitness versus physical activity patterns in predicting mortality in men. American Journal of Medicine. 2004;117(12):912–918.
    1. Brown WJ, McLaughlin D, Leung J, et al. Physical activity and all-cause mortality in older women and men. British Journal of Sports Medicine. 2012;46:664–668.
    1. DeSouza CA, Shapiro LF, Clevenger CM, et al. Regular aerobic exercise prevents and restores age-related declines in endothelium-dependent vasodilation in healthy men. Circulation. 2000;102(12):1351–1357.
    1. Taddei S, Galetta F, Virdis A, et al. Physical activity prevents age-related impairment in nitric oxide availability in elderly athletes. Circulation. 2000;101(25):2896–2901.
    1. Lauer T, Heiss C, Balzer J, et al. Age-dependent endothelial dysfunction is associated with failure to increase plasma nitrite in response to exercise. Basic Research in Cardiology. 2008;103(3):291–297.
    1. Franzoni F, Galetta F, Morizzo C, et al. Effects of age and physical fitness on microcirculatory function. Clinical Science. 2004;106(3):329–335.
    1. Karolkiewicz J, Szczêsniak L, Deskur-Smielecka E, Nowak A, Stemplewski R, Szeklicki R. Oxidative stress and antioxidant defense system in healthy, elderly men: relationship to physical activity. Aging Male. 2003;6(2):100–105.
    1. Cheng X, Siow RCM, Mann GE. Impaired redox signaling and antioxidant gene expression in endothelial cells in diabetes: a role for mitochondria and the nuclear factor-E2-related factor 2-Kelch-like ECH-associated protein 1 defense pathway. Antioxidants and Redox Signaling. 2011;14(3):469–487.
    1. Bao W, Song F, Li X, et al. Plasma heme oxygenase-1 concentration is elevated in individuals with type 2 diabetes mellitus. PLoS One. 2010;5(8)e12371
    1. Babusikova E, Jesenak M, Durdik P, Dobrota D, Banovcin P. Exhaled carbon monoxide as a new marker of respiratory diseases in children. Journal of Physiology and Pharmacology. 2008;59(supplement 6):9–17.
    1. Vile GF, Tyrrell RM. Oxidative stress resulting from ultraviolet A irradiation of human skin fibroblasts leads to a heme oxygenase-dependent increase in ferritin. Journal of Biological Chemistry. 1993;268(20):14678–14681.
    1. Bélanger S, Lavoie J-C, Chessex P. Influence of bilirubin on the antioxidant capacity of plasma in newborn infants. Biology of the Neonate. 1997;71(4):233–238.
    1. Ryter SW, Alam J, Choi AMK. Heme oxygenase-1/carbon monoxide: from basic science to therapeutic applications. Physiological Reviews. 2006;86(2):583–650.
    1. Niess AM, Passek F, Lorenz I, et al. Expression of the antioxidant stress protein heme oxygenase-1 (HO-1) in human leukocytes: acute and adaptational responses to endurance exercise. Free Radical Biology and Medicine. 1999;26(1-2):184–192.
    1. Asghar M, George L, Lokhandwala MF. Exercise decreases oxidative stress and inflammation and restores renal dopamine D1 receptor function in old rats. American Journal of Physiology—Renal Physiology. 2007;293(3):F914–F919.
    1. Fleming I, Busse R. Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase. American Journal of Physiology—Regulatory Integrative and Comparative Physiology. 2003;284(1):R1–R12.
    1. Fukai T, Siegfried MR, Ushio-Fukai M, Cheng Y, Kojda G, Harrison DG. Regulation of the vascular extracellular superoxide dismutase by nitric oxide and exercise training. Journal of Clinical Investigation. 2000;105(11):631–1639.
    1. Kojda G, Cheng YC, Burchfield J, Harrison DG. Dysfunctional regulation of endothelial nitric oxide synthase (eNOS) expression in response to exercise in mice lacking one eNOS gene. Circulation. 2001;103(23):2839–2844.
    1. Hambrecht R, Adams V, Erbs S, et al. Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase. Circulation. 2003;107(25):3152–3158.
    1. Hambrecht R, Wolf A, Gielen S, et al. Effect of exercise on coronary endothelial function in patients with coronary artery disease. The New England Journal of Medicine. 2000;342(7):454–460.
    1. Hambrecht R, Gielen S, Linke A, et al. Effects of exercise training on left ventricular function and peripheral resistance in patients with chronic heart failure: a randomized trial. Journal of the American Medical Association. 2000;283(23):3095–3101.
    1. Johnson BD, Mather KJ, Wallace JP. Mechanotransduction of shear in the endothelium: basic studies and clinical implications. Vascular Medicine. 2011;16:365–377.
    1. Laurindo FRM, Pedro MDA, Barbeiro HV, et al. Vascular free radical release: ex vivo and in vivo evidence for a flow- dependent endothelial mechanism. Circulation Research. 1994;74(4):700–709.
    1. de Keulenaer GW, Chappell DC, Ishizaka N, Nerem RM, Alexander RW, Griendling KK. Oscillatory and steady laminar shear stress differentially affect human endothelial redox state: role of a superoxide-producing NADH oxidase. Circulation Research. 1998;82(10):1094–1101.
    1. Drummond GR, Cai H, Davis ME, Ramasamy S, Harrison DG. Transcriptional and posttranscriptional regulation of endothelial nitric oxide synthase expression by hydrogen peroxide. Circulation Research. 2000;86(3):347–354.
    1. Cai H, Davis ME, Drummond GR, Harrison DG. Induction of endothelial NO synthase by hydrogen peroxide via a Ca2+/calmodulin-dependent protein kinase II/janus kinase 2-dependent pathway. Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21(10):1571–1576.
    1. Rush JWE, Turk JR, Laughlin MH. Exercise training regulates SOD-1 and oxidative stress in porcine aortic endothelium. American Journal of Physiology—Heart and Circulatory Physiology. 2003;284(4):H1378–H1387.
    1. Maeda S, Sugawara J, Yoshizawa M, et al. Involvement of endothelin-1 in habitual exercise-induced increase in arterial compliance. Acta Physiologica. 2009;196(2):223–229.
    1. Kasapis C, Thompson PD. The effects of physical activity on serum C-reactive protein and inflammatory markers: a systematic review. Journal of the American College of Cardiology. 2005;45(10):1563–1569.
    1. Plaisance EP, Grandjean PW. Physical activity and high-sensitivity C-reactive protein. Sports Medicine. 2006;36(5):443–458.
    1. Fallon KE, Fallon SK, Boston T. The acute phase response and exercise: court and field sports. British Journal of Sports Medicine. 2001;35(3):170–173.
    1. Nieman DC, Davis JM, Henson DA, et al. Carbohydrate ingestion influences skeletal muscle cytokine mRNA and plasma cytokine levels after a 3-h run. Journal of Applied Physiology. 2003;94(5):1917–1925.
    1. Keller C, Steensberg A, Pilegaard H, et al. Transcriptional activation of the IL-6 gene in human contracting skeletal muscle: influence of muscle glycogen content. The FASEB Journal. 2001;15(14):2748–2750.
    1. Febbraio MA, Pedersen BK. Contraction-induced myokine production and release: is skeletal muscle an endocrine organ? Exercise and Sport Sciences Reviews. 2005;33(3):114–119.
    1. Nielsen AR, Mounier R, Plomgaard P, et al. Expression of interleukin-15 in human skeletal muscle effect of exercise and muscle fibre type composition. Journal of Physiology. 2007;584(1):305–312.
    1. Pedersen BK, Febbraio MA. Point: interleukin-6 does have a beneficial role in insulin sensitivity and glucose homeostasis. Journal of Applied Physiology. 2007;102(2):814–819.
    1. Pedersen BK, Bruunsgaard H. Possible beneficial role of exercise in modulating low-grade inflammation in the elderly. Scandinavian Journal of Medicine and Science in Sports. 2003;13(1):56–62.
    1. Festa A, D’Agostino R, Jr., Howard G, Mykkänen L, Tracy RP, Haffner SM. Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS) Circulation. 2000;102(1):42–47.
    1. Starkie R, Ostrowski SR, Jauffred S, Febbraio M, Pedersen BK. Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans. The FASEB Journal. 2003;17(8):884–886.
    1. Keller C, Keller P, Giralt M, Hidalgo J, Pedersen BK. Exercise normalises overexpression of TNF-α in knockout mice. Biochemical and Biophysical Research Communications. 2004;321(1):179–182.
    1. van der Poll T, Coyle SM, Barbosa K, Braxton CC, Lowry SF. Epinephrine inhibits tumor necrosis factor-α and potentiates interleukin 10 production during human endotoxemia. Journal of Clinical Investigation. 1996;97(3):713–719.
    1. Petersen EW, Carey AL, Sacchetti M, et al. Acute IL-6 treatment increases fatty acid turnover in elderly humans in vivo and in tissue culture in vitro. American Journal of Physiology—Endocrinology and Metabolism. 2005;288(1):E155–E162.
    1. Wallenius V, Wallenius K, Ahrén B, et al. Interleukin-6-deficient mice develop mature-onset obesity. Nature Medicine. 2002;8(1):75–79.
    1. van Hall G, Steensberg A, Sacchetti M, et al. Interleukin-6 stimulates lipolysis and fat oxidation in humans. Journal of Clinical Endocrinology and Metabolism. 2003;88(7):3005–3010.
    1. Brandt C, Pedersen BK. The role of exercise-induced myokines in muscle homeostasis and the defense against chronic diseases. Journal of Biomedicine and Biotechnology. 2010;2010:6 pages.520258
    1. Hopps E, Canino B, Caimi G. Effects of exercise on inflammation markers in type 2 diabetic subjects. Acta Diabetologica. 2011;48(3):183–189.
    1. Quinn LS, Anderson BG, Drivdahl RH, Alvarez B, Argilés JM. Overexpression of interleukin-15 induces skeletal muscle hypertrophy in vitro: implications for treatment of muscle wasting disorders. Experimental Cell Research. 2002;280(1):55–63.
    1. Figueras M, Busquets S, Carbó N, et al. Interleukin-15 is able to suppress the increased DNA fragmentation associated with muscle wasting in tumour-bearing rats. FEBS Letters. 2004;569(1–3):201–206.
    1. Marzetti E, Groban L, Wohlgemuth SE, et al. Effects of short-term GH supplementation and treadmill exercise training on physical performance and skeletal muscle apoptosis in old rats. American Journal of Physiology—Regulatory Integrative and Comparative Physiology. 2008;294(2):R558–R567.
    1. Marzetti E, Lawler JM, Hiona A, Manini T, Seo AY, Leeuwenburgh C. Modulation of age-induced apoptotic signaling and cellular remodeling by exercise and calorie restriction in skeletal muscle. Free Radical Biology and Medicine. 2008;44(2):160–168.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren