Cardiovascular Effects and Benefits of Exercise

Matthew A Nystoriak, Aruni Bhatnagar, Matthew A Nystoriak, Aruni Bhatnagar

Abstract

It is widely accepted that regular physical activity is beneficial for cardiovascular health. Frequent exercise is robustly associated with a decrease in cardiovascular mortality as well as the risk of developing cardiovascular disease. Physically active individuals have lower blood pressure, higher insulin sensitivity, and a more favorable plasma lipoprotein profile. Animal models of exercise show that repeated physical activity suppresses atherogenesis and increases the availability of vasodilatory mediators such as nitric oxide. Exercise has also been found to have beneficial effects on the heart. Acutely, exercise increases cardiac output and blood pressure, but individuals adapted to exercise show lower resting heart rate and cardiac hypertrophy. Both cardiac and vascular changes have been linked to a variety of changes in tissue metabolism and signaling, although our understanding of the contribution of the underlying mechanisms remains incomplete. Even though moderate levels of exercise have been found to be consistently associated with a reduction in cardiovascular disease risk, there is evidence to suggest that continuously high levels of exercise (e.g., marathon running) could have detrimental effects on cardiovascular health. Nevertheless, a specific dose response relationship between the extent and duration of exercise and the reduction in cardiovascular disease risk and mortality remains unclear. Further studies are needed to identify the mechanisms that impart cardiovascular benefits of exercise in order to develop more effective exercise regimens, test the interaction of exercise with diet, and develop pharmacological interventions for those unwilling or unable to exercise.

Keywords: atherosclerosis; blood flow; coronary artery disease; endothelium; physical activity.

Figures

Figure 1
Figure 1
Overview of major cardiovascular effects of exercise. Abbreviations: HR, heart rate; LV, left ventricle; eNOS, endothelial nitric oxide synthase; NO, nitric oxide; VSM, vascular smooth muscle; BP, blood pressure; HDL, high density lipoprotein; LDL, low density lipoprotein; VLDL, very low density lipoprotein; TG, triglycerides; EPC, endothelial progenitor cell.

References

    1. CDC N (2015). Underlying Cause of Death 1999-2013 on CDC WONDER Online Database, Released 2015. Data are From the Multiple Cause of Death Files, 1999-2013, as Compiled From Data Provided by the 57 Vital Statistics Jurisdictions Through the Vital Statistics Cooperative Program (Accessed Feb. 3, 2015).
    1. Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, et al. . Heart disease and stroke statistics-2017 update: a report from the American Heart Association. Circulation (2017) 135:e146–603. 10.1161/CIR.0000000000000485
    1. Roth GA, Forouzanfar MH, Moran AE, Barber R, Nguyen G, Feigin VL, et al. . Demographic and epidemiologic drivers of global cardiovascular mortality. N Engl J Med. (2015) 372:1333–41. 10.1056/NEJMoa1406656
    1. Paffenbarger RS, Jr, Hyde RT, Wing AL, Hsieh CC. Physical activity, all-cause mortality, and longevity of college alumni. N Engl J Med. (1986) 314:605–13. 10.1056/NEJM198603063141003
    1. Blair SN, Kampert JB, Kohl HW, III, Barlow CE, Macera CA, Paffenbarger RS, Jr, et al. . Influences of cardiorespiratory fitness and other precursors on cardiovascular disease and all-cause mortality in men and women. JAMA (1996) 276:205–10. 10.1001/jama.1996.03540030039029
    1. Stevens J, Cai J, Evenson KR, Thomas R. Fitness and fatness as predictors of mortality from all causes and from cardiovascular disease in men and women in the lipid research clinics study. Am J Epidemiol. (2002) 156:832–41. 10.1093/aje/kwf114
    1. Hu FB, Willett WC, Li T, Stampfer MJ, Colditz GA, Manson JE. Adiposity as compared with physical activity in predicting mortality among women. N Engl J Med. (2004) 351:2694–703. 10.1056/NEJMoa042135
    1. Vella CA, Allison MA, Cushman M, Jenny NS, Miles MP, Larsen B, et al. . Physical activity and adiposity-related inflammation: the MESA. Med Sci Sports Exerc. (2017) 49:915–21. 10.1249/MSS.0000000000001179
    1. Florido R, Kwak L, Lazo M, Nambi V, Ahmed HM, Hegde SM, et al. . Six-year changes in physical activity and the risk of incident heart failure: ARIC study. Circulation (2018) 137:2142–51. 10.1161/CIRCULATIONAHA.117.030226
    1. Moholdt T, Lavie CJ, Nauman J. Sustained physical activity, not weight loss, associated with improved survival in coronary heart disease. J Am Coll Cardiol. (2018) 71:1094–101. 10.1016/j.jacc.2018.01.011
    1. Caspersen CJ, Powell KE, Christenson GM. Physical activity, exercise, and physical fitness: definitions and distinctions for health-related research. Public Health Rep. (1985) 100:126–31.
    1. Haskell WL. The influence of exercise on the concentrations of triglyceride and cholesterol in human plasma. Exerc Sport Sci Rev. (1984) 12:205–44. 10.1249/00003677-198401000-00009
    1. Fuster V, Gotto AM, Libby P, Loscalzo J, McGill HC. 27th Bethesda Conference: matching the intensity of risk factor management with the hazard for coronary disease events. Task Force 1. Pathogenesis of coronary disease: the biologic role of risk factors. J Am Coll Cardiol. (1996) 27:964–76. 10.1016/0735-1097(96)00014-9
    1. Leon AS, Sanchez OA. Response of blood lipids to exercise training alone or combined with dietary intervention. Med Sci Sports Exerc. (2001) 33(Suppl. 6):S502–15; discussion S528–509. 10.1097/00005768-200106001-00021
    1. Kraus WE, Houmard JA, Duscha BD, Knetzger KJ, Wharton MB, McCartney JS, et al. . Effects of the amount and intensity of exercise on plasma lipoproteins. N Engl J Med. (2002) 347:1483–92. 10.1056/NEJMoa020194
    1. Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med. (1977) 62:707–14. 10.1016/0002-9343(77)90874-9
    1. Assmann G, Schulte H. Relation of high-density lipoprotein cholesterol and triglycerides to incidence of atherosclerotic coronary artery disease (the PROCAM experience). Prospective Cardiovascular Munster study. Am J Cardiol. (1992) 70:733–7. 10.1016/0002-9149(92)90550-I
    1. Schwartz GG, Olsson AG, Abt M, Ballantyne CM, Barter PJ, Brumm J, et al. . Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. (2012) 367:2089–99. 10.1056/NEJMoa1206797
    1. Group HTC, Landray MJ, Haynes R, Hopewell JC, Parish S, Aung T, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. (2014) 371:203–12. 10.1056/NEJMoa1300955
    1. Du XM, Kim MJ, Hou L, Le Goff W, Chapman MJ, Van Eck M, et al. . HDL particle size is a critical determinant of ABCA1-mediated macrophage cellular cholesterol export. Circ Res. (2015) 116:1133–42. 10.1161/CIRCRESAHA.116.305485
    1. Sarzynski MA, Ruiz-Ramie JJ, Barber JL, Slentz CA, Apolzan JW, McGarrah RW, et al. . Effects of increasing exercise intensity and dose on multiple measures of HDL (High-Density Lipoprotein) function. Arterioscler Thromb Vasc Biol. (2018) 38:943–52. 10.1161/ATVBAHA.117.310307
    1. Lee IM, Paffenbarger RS, Jr, Hennekens CH. Physical activity, physical fitness and longevity. Aging (1997) 9:2–11. 10.1007/BF03340123
    1. Sesso HD, Paffenbarger RS, Jr, Lee IM. Physical activity and coronary heart disease in men: the Harvard Alumni Health Study. Circulation (2000) 102:975–80. 10.1161/01.CIR.102.9.975
    1. Blair SN, Jackson AS. Physical fitness and activity as separate heart disease risk factors: a meta-analysis. Med Sci Sports Exerc. (2001) 33:762–4. 10.1097/00005768-200105000-00013
    1. Thompson PD, Buchner D, Pina IL, Balady GJ, Williams MA, Marcus BH, et al. . Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity). Circulation (2003) 107:3109–16. 10.1161/01.CIR.0000075572.40158.77
    1. Hambrecht R, Niebauer J, Marburger C, Grunze M, Kalberer B, Hauer K, et al. . Various intensities of leisure time physical activity in patients with coronary artery disease: effects on cardiorespiratory fitness and progression of coronary atherosclerotic lesions. J Am Coll Cardiol. (1993) 22:468–77. 10.1016/0735-1097(93)90051-2
    1. Hambrecht R, Adams V, Erbs S, Linke A, Krankel N, Shu Y, et al. . Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase. Circulation (2003) 107:3152–8. 10.1161/01.CIR.0000074229.93804.5C
    1. Pynn M, Schafer K, Konstantinides S, Halle M. Exercise training reduces neointimal growth and stabilizes vascular lesions developing after injury in apolipoprotein e-deficient mice. Circulation (2004) 109:386–92. 10.1161/01.CIR.0000109500.03050.7C
    1. Laufs U, Wassmann S, Czech T, Munzel T, Eisenhauer M, Bohm M, et al. . Physical inactivity increases oxidative stress, endothelial dysfunction, and atherosclerosis. Arterioscler Thromb Vasc Biol. (2005) 25:809–14. 10.1161/
    1. Matsumoto Y, Adams V, Jacob S, Mangner N, Schuler G, Linke A. Regular exercise training prevents aortic valve disease in low-density lipoprotein-receptor-deficient mice. Circulation (2010) 121:759–67. 10.1161/CIRCULATIONAHA.109.892224
    1. Ginsberg HN. Insulin resistance and cardiovascular disease. J Clin Invest. (2000) 106:453–8. 10.1172/JCI10762
    1. Lewis GF. Fatty acid regulation of very low density lipoprotein production. Curr Opin Lipidol. (1997) 8:146–53. 10.1097/00041433-199706000-00004
    1. Borggreve SE, De Vries R, Dullaart RP. Alterations in high-density lipoprotein metabolism and reverse cholesterol transport in insulin resistance and type 2 diabetes mellitus: role of lipolytic enzymes, lecithin:cholesterol acyltransferase and lipid transfer proteins. Eur J Clin Invest. (2003) 33:1051–69. 10.1111/j.1365-2362.2003.01263.x
    1. Steinberg HO, Brechtel G, Johnson A, Fineberg N, Baron AD. Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. J Clin Invest. (1994) 94:1172–9. 10.1172/JCI117433
    1. Zeng G, Quon MJ. Insulin-stimulated production of nitric oxide is inhibited by wortmannin. Direct measurement in vascular endothelial cells. J Clin Invest. (1996) 98:894–8. 10.1172/JCI118871
    1. Potenza MA, Marasciulo FL, Chieppa DM, Brigiani GS, Formoso G, Quon MJ, et al. . Insulin resistance in spontaneously hypertensive rats is associated with endothelial dysfunction characterized by imbalance between NO and ET-1 production. Am J Physiol Heart Circ Physiol. (2005) 289:H813–22. 10.1152/ajpheart.00092.2005
    1. Marasciulo FL, Montagnani M, Potenza MA. Endothelin-1: the yin and yang on vascular function. Curr Med Chem. (2006) 13:1655–65. 10.2174/092986706777441968
    1. Beckman JA, Creager MA, Libby P. Diabetes and atherosclerosis: epidemiology, pathophysiology, and management. JAMA (2002) 287:2570–81. 10.1001/jama.287.19.2570
    1. Wang CC, Gurevich I, Draznin B. Insulin affects vascular smooth muscle cell phenotype and migration via distinct signaling pathways. Diabetes (2003) 52:2562–9. 10.2337/diabetes.52.10.2562
    1. Schleicher ED, Wagner E, Nerlich AG. Increased accumulation of the glycoxidation product N(epsilon)-(carboxymethyl)lysine in human tissues in diabetes and aging. J Clin Invest. (1997) 99:457–68. 10.1172/JCI119180
    1. Sell DR, Monnier VM. Molecular basis of arterial stiffening: role of glycation - a mini-review. Gerontology (2012) 58:227–37. 10.1159/000334668
    1. Wallberg-Henriksson H, Gunnarsson R, Henriksson J, DeFronzo R, Felig P, Ostman J, et al. . Increased peripheral insulin sensitivity and muscle mitochondrial enzymes but unchanged blood glucose control in type I diabetics after physical training. Diabetes (1982) 31:1044–50. 10.2337/diacare.31.12.1044
    1. Trovati M, Carta Q, Cavalot F, Vitali S, Banaudi C, Lucchina PG, et al. . Influence of physical training on blood glucose control, glucose tolerance, insulin secretion, and insulin action in non-insulin-dependent diabetic patients. Diabetes Care (1984) 7:416–20. 10.2337/diacare.7.5.416
    1. Koivisto VA, Yki-Jarvinen H, DeFronzo RA. Physical training and insulin sensitivity. Diabetes Metab Rev (1986) 1:445–81. 10.1002/dmr.5610010407
    1. Newsom SA, Everett AC, Hinko A, Horowitz JF. A single session of low-intensity exercise is sufficient to enhance insulin sensitivity into the next day in obese adults. Diabetes Care (2013) 36:2516–22. 10.2337/dc12-2606
    1. Richter EA, Garetto LP, Goodman MN, Ruderman NB. Muscle glucose metabolism following exercise in the rat: increased sensitivity to insulin. J Clin Invest. (1982) 69:785–93. 10.1172/JCI110517
    1. Craig BW, Garthwaite SM, Holloszy JO. Adipocyte insulin resistance: effects of aging, obesity, exercise, and food restriction. J Appl Physiol. (1987) 62:95–100. 10.1152/jappl.1987.62.1.95
    1. Zheng C, Liu Z. Vascular function, insulin action, and exercise: an intricate interplay. Trends Endocrinol Metab. (2015) 26:297–304. 10.1016/j.tem.2015.02.002
    1. Olver TD, McDonald MW, Klakotskaia D, Richardson RA, Jasperse JL, Melling CWJ, et al. . A chronic physical activity treatment in obese rats normalizes the contributions of ET-1 and NO to insulin-mediated posterior cerebral artery vasodilation. J Appl Physiol. (2017) 122:1040–50. 10.1152/japplphysiol.00811.2016
    1. Kim Y, Inoue T, Nakajima R, Nakae K, Tamura T, Tokuyama K, et al. . Effects of endurance training on gene expression of insulin signal transduction pathway. Biochem Biophys Res Commun. (1995) 210:766–73. 10.1006/bbrc.1995.1725
    1. Houmard JA, Shaw CD, Hickey MS, Tanner CJ. Effect of short-term exercise training on insulin-stimulated PI 3-kinase activity in human skeletal muscle. Am J Physiol. (1999) 277(6 Pt 1):E1055–60. 10.1152/ajpendo.1999.277.6.E1055
    1. Kirwan JP, del Aguila LF, Hernandez JM, Williamson DL, O'Gorman DJ, Lewis R, et al. . Regular exercise enhances insulin activation of IRS-1-associated PI3-kinase in human skeletal muscle. J Appl Physiol (2000) 88:797–803. 10.1152/jappl.2000.88.2.797
    1. Richter EA, Mikines KJ, Galbo H, Kiens B. Effect of exercise on insulin action in human skeletal muscle. J Appl Physiol. (1989) 66:876–85. 10.1152/jappl.1989.66.2.876
    1. Goodyear LJ, King PA, Hirshman MF, Thompson CM, Horton ED, Horton ES. Contractile activity increases plasma membrane glucose transporters in absence of insulin. Am J Physiol. (1990) 258(4 Pt 1):E667–72. 10.1152/ajpendo.1990.258.4.E667
    1. Gao J, Ren J, Gulve EA, Holloszy JO. Additive effect of contractions and insulin on GLUT-4 translocation into the sarcolemma. J Appl Physiol. (1994) 77:1597–601. 10.1152/jappl.1994.77.4.1597
    1. Hotamisligil GS, Murray DL, Choy LN, Spiegelman BM. Tumor necrosis factor alpha inhibits signaling from the insulin receptor. Proc Natl Acad Sci USA. (1994) 91:4854–8. 10.1073/pnas.91.11.4854
    1. del Aguila LF, Claffey KP, Kirwan JP. TNF-alpha impairs insulin signaling and insulin stimulation of glucose uptake in C2C12 muscle cells. Am J Physiol. (1999) 276(Pt 1):E849–55.
    1. Del Aguila LF, Krishnan RK, Ulbrecht JS, Farrell PA, Correll PH, Lang CH, et al. . Muscle damage impairs insulin stimulation of IRS-1, PI 3-kinase, and Akt-kinase in human skeletal muscle. Am J Physiol Endocrinol Metab. (2000) 279:E206–12. 10.1152/ajpendo.2000.279.1.E206
    1. Kirwan JP, del Aguila LF. Insulin signalling, exercise and cellular integrity. Biochem Soc Trans. (2003). 31(Pt 6):1281–5. 10.1042/bst0311281
    1. Shepherd JT. Circulatory response to exercise in health. Circulation (1987) 76(Pt 2):VI3–10.
    1. Fagard RH. Exercise characteristics and the blood pressure response to dynamic physical training. Med Sci Sports Exerc. (2001) 33(Suppl. 6):S484–92; discussion S493–484. 10.1097/00005768-200106001-00018
    1. Hardy ST, Loehr LR, Butler KR, Chakladar S, Chang PP, Folsom AR, et al. . Reducing the blood pressure-related burden of cardiovascular disease: impact of achievable improvements in blood pressure prevention and control. J Am Heart Assoc. (2015) 4:e002276. 10.1161/JAHA.115.002276
    1. Cox KL, Puddey IB, Morton AR, Burke V, Beilin LJ, McAleer M. Exercise and weight control in sedentary overweight men: effects on clinic and ambulatory blood pressure. J Hypertens. (1996) 14:779–90. 10.1097/00004872-199606000-00015
    1. Bacon SL, Sherwood A, Hinderliter A, Blumenthal JA. Effects of exercise, diet and weight loss on high blood pressure. Sports Med. (2004) 34:307–16. 10.2165/00007256-200434050-00003
    1. Fagard RH. Exercise is good for your blood pressure: effects of endurance training and resistance training. Clin Exp Pharmacol Physiol. (2006) 33:853–6. 10.1111/j.1440-1681.2006.04453.x
    1. Niebauer J, Cooke JP. Cardiovascular effects of exercise: role of endothelial shear stress. J Am Coll Cardiol. (1996) 28:1652–60. 10.1016/S0735-1097(96)00393-2
    1. Dominiczak AF, Bohr DF. Nitric oxide and its putative role in hypertension. Hypertension (1995) 25:1202–11. 10.1161/01.HYP.25.6.1202
    1. Kim IJ, Bae J, Lim SW, Cha DH, Cho HJ, Kim S, et al. . Influence of endothelial nitric oxide synthase gene polymorphisms (-786T>C, 4a4b, 894G>T) in Korean patients with coronary artery disease. Thromb Res. (2007) 119:579–85. 10.1016/j.thromres.2006.06.005
    1. Cruz-Gonzalez I, Corral E, Sanchez-Ledesma M, Sanchez-Rodriguez A, Martin-Luengo C, Gonzalez-Sarmiento R. Association between -T786C NOS3 polymorphism and resistant hypertension: a prospective cohort study. BMC Cardiovasc Disord. (2009) 9:35. 10.1186/1471-2261-9-35
    1. Zago AS, Park JY, Fenty-Stewart N, Kokubun E, Brown MD. Effects of aerobic exercise on the blood pressure, oxidative stress and eNOS gene polymorphism in pre-hypertensive older people. Eur J Appl Physiol. (2010) 110:825–32. 10.1007/s00421-010-1568-6
    1. Kuru O, Senturk UK, Kocer G, Ozdem S, Baskurt OK, Cetin A, et al. . Effect of exercise training on resistance arteries in rats with chronic NOS inhibition. J Appl Physiol. (2009) 107:896–902. 10.1152/japplphysiol.91180.2008
    1. Wilund KR. Is the anti-inflammatory effect of regular exercise responsible for reduced cardiovascular disease? Clin Sci. (2007) 112:543–55. 10.1042/CS20060368
    1. Fleenor BS, Marshall KD, Durrant JR, Lesniewski LA, Seals DR. Arterial stiffening with ageing is associated with transforming growth factor-beta1-related changes in adventitial collagen: reversal by aerobic exercise. J Physiol. (2010) 588(Pt 20):3971–82. 10.1113/jphysiol.2010.194753
    1. Carter JR, Ray CA. Sympathetic neural adaptations to exercise training in humans. Auton Neurosci. (2015) 188:36–43. 10.1016/j.autneu.2014.10.020
    1. Breisch EA, White FC, Nimmo LE, McKirnan MD, Bloor CM. Exercise-induced cardiac hypertrophy: a correlation of blood flow and microvasculature. J Appl Physiol. (1986) 60:1259–67. 10.1152/jappl.1986.60.4.1259
    1. Borlaug BA, Lam CS, Roger VL, Rodeheffer RJ, Redfield MM. Contractility and ventricular systolic stiffening in hypertensive heart disease insights into the pathogenesis of heart failure with preserved ejection fraction. J Am Coll Cardiol. (2009) 54:410–8. 10.1016/j.jacc.2009.05.013
    1. Burelle Y, Wambolt RB, Grist M, Parsons HL, Chow JC, Antler C, et al. . Regular exercise is associated with a protective metabolic phenotype in the rat heart. Am J Physiol Heart Circ Physiol. (2004) 287:H1055–63. 10.1152/ajpheart.00925.2003
    1. Riehle C, Wende AR, Zhu Y, Oliveira KJ, Pereira RO, Jaishy BP, et al. . Insulin receptor substrates are essential for the bioenergetic and hypertrophic response of the heart to exercise training. Mol Cell Biol. (2014) 34:3450–60. 10.1128/MCB.00426-14
    1. Gibb AA, Epstein PN, Uchida S, Zheng Y, McNally LA, Obal D, et al. . Exercise-induced changes in glucose metabolism promote physiological cardiac growth. Circulation (2017) 136:2144–57. 10.1161/CIRCULATIONAHA.117.028274
    1. McMullen JR, Shioi T, Huang WY, Zhang L, Tarnavski O, Bisping E, et al. . The insulin-like growth factor 1 receptor induces physiological heart growth via the phosphoinositide 3-kinase(p110alpha) pathway. J Biol Chem. (2004) 279:4782–93. 10.1074/jbc.M310405200
    1. Kim J, Wende AR, Sena S, Theobald HA, Soto J, Sloan C, et al. . Insulin-like growth factor I receptor signaling is required for exercise-induced cardiac hypertrophy. Mol Endocrinol. (2008) 22:2531–43. 10.1210/me.2008-0265
    1. Bostrom P, Mann N, Wu J, Quintero PA, Plovie ER, Panakova D, et al. . C/EBPbeta controls exercise-induced cardiac growth and protects against pathological cardiac remodeling. Cell (2010) 143:1072–83. 10.1016/j.cell.2010.11.036
    1. Bezzerides VJ, Platt C, Lerchenmuller C, Paruchuri K, Oh NL, Xiao C, et al. . CITED4 induces physiologic hypertrophy and promotes functional recovery after ischemic injury. JCI Insight (2016) 1:e85904. 10.1172/jci.insight.85904
    1. Wilkins BJ, Dai YS, Bueno OF, Parsons SA, Xu J, Plank DM, et al. Calcineurin/NFAT coupling participates in pathological, but not physiological, cardiac hypertrophy. Circ Res. (2004) 94:110–8. 10.1161/01.RES.0000109415.17511.18
    1. Ferguson S, Gledhill N, Jamnik VK, Wiebe C, Payne N. Cardiac performance in endurance-trained and moderately active young women. Med Sci Sports Exerc. (2001) 33:1114–9. 10.1097/00005768-200107000-00008
    1. Esch BT, Scott JM, Haykowsky MJ, McKenzie DC, Warburton DE. Diastolic ventricular interactions in endurance-trained athletes during orthostatic stress. Am J Physiol Heart Circ Physiol. (2007) 293:H409–15. 10.1152/ajpheart.00928.2006
    1. Moore RL, Musch TI, Yelamarty RV, Scaduto RC, Jr, Semanchick AM, Elensky M, et al. . Chronic exercise alters contractility and morphology of isolated rat cardiac myocytes. Am J Physiol. (1993) 264(5 Pt 1):C1180–9. 10.1152/ajpcell.1993.264.5.C1180
    1. Wisloff U, Loennechen JP, Currie S, Smith GL, Ellingsen O. Aerobic exercise reduces cardiomyocyte hypertrophy and increases contractility, Ca2+ sensitivity and SERCA-2 in rat after myocardial infarction. Cardiovasc Res. (2002) 54:162–74. 10.1016/S0008-6363(01)00565-X
    1. Diffee GM, Chung E. Altered single cell force-velocity and power properties in exercise-trained rat myocardium. J Appl Physiol. (2003) 94:1941–8. 10.1152/japplphysiol.00889.2002
    1. Kemi OJ, Ellingsen O, Smith GL, Wisloff U. Exercise-induced changes in calcium handling in left ventricular cardiomyocytes. Front Biosci. (2008) 13:356–68. 10.2741/2685
    1. Natali AJ, Wilson LA, Peckham M, Turner DL, Harrison SM, White E. Different regional effects of voluntary exercise on the mechanical and electrical properties of rat ventricular myocytes. J Physiol. (2002) 541(Pt 3):863–75. 10.1113/jphysiol.2001.013415
    1. Kemi OJ, Wisloff U. Mechanisms of exercise-induced improvements in the contractile apparatus of the mammalian myocardium. Acta Physiol. (2010) 199:425–39. 10.1111/j.1748-1716.2010.02132.x
    1. Wisloff U, Loennechen JP, Falck G, Beisvag V, Currie S, Smith G, et al. . Increased contractility and calcium sensitivity in cardiac myocytes isolated from endurance trained rats. Cardiovasc Res. (2001) 50:495–508. 10.1016/S0008-6363(01)00210-3
    1. Marionneau C, Brunet S, Flagg TP, Pilgram TK, Demolombe S, Nerbonne JM. Distinct cellular and molecular mechanisms underlie functional remodeling of repolarizing K+ currents with left ventricular hypertrophy. Circ Res. (2008) 102:1406–15. 10.1161/CIRCRESAHA.107.170050
    1. Biffi A, Maron BJ, Di Giacinto B, Porcacchia P, Verdile L, Fernando F, et al. . Relation between training-induced left ventricular hypertrophy and risk for ventricular tachyarrhythmias in elite athletes. Am J Cardiol. (2008) 101:1792–5. 10.1016/j.amjcard.2008.02.081
    1. Yang KC, Foeger NC, Marionneau C, Jay PY, McMullen JR, Nerbonne JM. Homeostatic regulation of electrical excitability in physiological cardiac hypertrophy. J Physiol. (2010) 588(Pt 24):5015–32. 10.1113/jphysiol.2010.197418
    1. Yang KC, Tseng YT, Nerbonne JM. Exercise training and PI3Kalpha-induced electrical remodeling is independent of cellular hypertrophy and Akt signaling. J Mol Cell Cardiol. (2012) 53:532–41. 10.1016/j.yjmcc.2012.07.004
    1. Buick FJ, Gledhill N, Froese AB, Spriet L, Meyers EC. Effect of induced erythrocythemia on aerobic work capacity. J Appl Physiol Respir Environ Exerc Physiol. (1980) 48:636–42. 10.1152/jappl.1980.48.4.636
    1. Weight LM, Klein M, Noakes TD, Jacobs P. 'Sports anemia'–a real or apparent phenomenon in endurance-trained athletes? Int J Sports Med. (1992) 13:344–7. 10.1055/s-2007-1021278
    1. Mairbaurl H. Red blood cells in sports: effects of exercise and training on oxygen supply by red blood cells. Front Physiol. (2013) 4:332. 10.3389/fphys.2013.00332
    1. Semenza GL. Regulation of oxygen homeostasis by hypoxia-inducible factor 1. Physiology (2009) 24:97–106. 10.1152/physiol.00045.2008
    1. Bonsignore MR, Morici G, Santoro A, Pagano M, Cascio L, Bonanno A, et al. . Circulating hematopoietic progenitor cells in runners. J Appl Physiol. (2002) 93:1691–7. 10.1152/japplphysiol.00376.2002
    1. Morici G, Zangla D, Santoro A, Pelosi E, Petrucci E, Gioia M, et al. . Supramaximal exercise mobilizes hematopoietic progenitors and reticulocytes in athletes. Am J Physiol Regul Integr Comp Physiol. (2005) 289:R1496–503. 10.1152/ajpregu.00338.2005
    1. Dufaux B, Order U. Plasma elastase-alpha 1-antitrypsin, neopterin, tumor necrosis factor, and soluble interleukin-2 receptor after prolonged exercise. Int J Sports Med. (1989) 10:434–8. 10.1055/s-2007-1024939
    1. Ostrowski K, Rohde T, Asp S, Schjerling P, Pedersen BK. Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans. J Physiol. (1999) 515 (Pt 1):287–91. 10.1111/j.1469-7793.1999.287ad.x
    1. Suzuki K, Yamada M, Kurakake S, Okamura N, Yamaya K, Liu Q, et al. . Circulating cytokines and hormones with immunosuppressive but neutrophil-priming potentials rise after endurance exercise in humans. Eur J Appl Physiol. (2000) 81:281–7. 10.1007/s004210050044
    1. Van Craenenbroeck EM, Vrints CJ, Haine SE, Vermeulen K, Goovaerts I, Van Tendeloo VF, et al. . A maximal exercise bout increases the number of circulating CD34+/KDR+ endothelial progenitor cells in healthy subjects. Relation with lipid profile. J Appl Physiol. (2008) 104:1006–13. 10.1152/japplphysiol.01210.2007
    1. Ribeiro F, Ribeiro IP, Goncalves AC, Alves AJ, Melo E, Fernandes R, et al. . Effects of resistance exercise on endothelial progenitor cell mobilization in women. Sci Rep. (2017) 7:17880. 10.1038/s41598-017-18156-6
    1. Green DJ, Hopman MT, Padilla J, Laughlin MH, Thijssen DH. Vascular Adaptation to Exercise in Humans: Role of Hemodynamic Stimuli. Physiol Rev. (2017) 97:495–528. 10.1152/physrev.00014.2016
    1. Hallen J. K+ balance in humans during exercise. Acta Physiol Scand. (1996) 156:279–86. 10.1046/j.1365-201X.1996.187000.x
    1. Radegran G, Calbet JA. Role of adenosine in exercise-induced human skeletal muscle vasodilatation. Acta Physiol Scand. (2001) 171:177–85. 10.1046/j.1365-201x.2001.00796.x
    1. Sarelius I, Pohl U. Control of muscle blood flow during exercise: local factors and integrative mechanisms. Acta Physiol. (2010) 199:349–65. 10.1111/j.1748-1716.2010.02129.x
    1. Sun D, Huang A, Koller A, Kaley G. Short-term daily exercise activity enhances endothelial NO synthesis in skeletal muscle arterioles of rats. J Appl Physiol. (1994) 76:2241–7. 10.1152/jappl.1994.76.5.2241
    1. Huonker M, Schmid A, Schmidt-Trucksass A, Grathwohl D, Keul J. Size and blood flow of central and peripheral arteries in highly trained able-bodied and disabled athletes. J Appl Physiol. (2003) 95:685–91. 10.1152/japplphysiol.00710.2001
    1. Joyner MJ, Casey DP. Regulation of increased blood flow (hyperemia) to muscles during exercise: a hierarchy of competing physiological needs. Physiol Rev. (2015) 95:549–601. 10.1152/physrev.00035.2013
    1. Laughlin MH, Yang HT, Tharp DL, Rector RS, Padilla J, Bowles DK. Vascular cell transcriptomic changes to exercise training differ directionally along and between skeletal muscle arteriolar trees. Microcirculation (2017) 24:e12336. 10.1111/micc.12336
    1. Taddei S, Galetta F, Virdis A, Ghiadoni L, Salvetti G, Franzoni F, et al. . Physical activity prevents age-related impairment in nitric oxide availability in elderly athletes. Circulation (2000) 101:2896–901. 10.1161/01.CIR.101.25.2896
    1. Feigl EO. Coronary physiology. Physiol Rev. (1983) 63:1–205. 10.1152/physrev.1983.63.1.1
    1. Heiss HW, Barmeyer J, Wink K, Hell G, Cerny FJ, Keul J, et al. . Studies on the regulation of myocardial blood flow in man. I: Training effects on blood flow and metabolism of the healthy heart at rest and during standardized heavy exercise Basic Res Cardiol. (1976) 71:658–75. 10.1007/BF01906411
    1. Barnard RJ, Duncan HW, Baldwin KM, Grimditch G, Buckberg GD. Effects of intensive exercise training on myocardial performance and coronary blood flow. J Appl Physiol Respir Environ Exerc Physiol. (1980) 49:444–9. 10.1152/jappl.1980.49.3.444
    1. Tomanek RJ. Effects of age and exercise on the extent of the myocardial capillary bed. Anat Rec. (1970) 167:55–62. 10.1002/ar.1091670106
    1. Thomas DP. Effects of acute and chronic exercise on myocardial ultrastructure. Med Sci Sports Exerc. (1985) 17:546–53. 10.1249/00005768-198510000-00007
    1. White FC, Bloor CM, McKirnan MD, Carroll SM. Exercise training in swine promotes growth of arteriolar bed and capillary angiogenesis in heart. J Appl Physiol. (1998) 85:1160–8. 10.1152/jappl.1998.85.3.1160
    1. Mobius-Winkler S, Uhlemann M, Adams V, Sandri M, Erbs S, Lenk K, et al. . Coronary Collateral growth induced by physical exercise: results of the impact of intensive exercise training on coronary collateral circulation in patients with stable coronary artery disease (EXCITE) trial. Circulation (2016) 133:1438–48; discussion 1448. 10.1161/CIRCULATIONAHA.115.016442
    1. DiCarlo SE, Blair RW, Bishop VS, Stone HL. Daily exercise enhances coronary resistance vessel sensitivity to pharmacological activation. J Appl Physiol. (1989) 66:421–8. 10.1152/jappl.1989.66.1.421
    1. Bowles DK, Laughlin MH, Sturek M. Exercise training increases K+-channel contribution to regulation of coronary arterial tone. J Appl Physiol. (1998) 84:1225–33. 10.1152/jappl.1998.84.4.1225
    1. Laughlin MH, Pollock JS, Amann JF, Hollis ML, Woodman CR, Price EM. Training induces nonuniform increases in eNOS content along the coronary arterial tree. J Appl Physiol. (2001) 90:501–10. 10.1152/jappl.2001.90.2.501
    1. Durand MJ, Dharmashankar K, Bian JT, Das E, Vidovich M, Gutterman DD, et al. Acute exertion elicits a H2O2-dependent vasodilator mechanism in the microvasculature of exercise-trained but not sedentary adults. Hypertension (2015) 65:140–5. 10.1161/HYPERTENSIONAHA.114.04540
    1. Robinson AT, Franklin NC, Norkeviciute E, Bian JT, Babana JC, Szczurek MR, et al. . Improved arterial flow-mediated dilation after exertion involves hydrogen peroxide in overweight and obese adults following aerobic exercise training. J Hypertens. (2016) 34:1309–16. 10.1097/HJH.0000000000000946
    1. Simpson ME, Serdula M, Galuska DA, Gillespie C, Donehoo R, Macera C, et al. . Walking trends among U.S. adults: the Behavioral Risk Factor Surveillance System, 1987-2000. Am J Prev Med. (2003) 25:95–100. 10.1016/S0749-3797(03)00112-0
    1. Wen CP, Wai JP, Tsai MK, Yang YC, Cheng TY, Lee MC, et al. . Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study. Lancet (2011) 378:1244–53. 10.1016/S0140-6736(11)60749-6
    1. O'Keefe JH, Patil HR, Lavie CJ, Magalski A, Vogel RA, McCullough PA. Potential adverse cardiovascular effects from excessive endurance exercise. Mayo Clin Proc. (2012) 87:587–95. 10.1016/j.mayocp.2012.04.005
    1. Roberts WO, Schwartz RS, Garberich RF, Carlson S, Knickelbine T, Schwartz JG, et al. . Fifty men, 3510 marathons, cardiac risk factors, and coronary artery calcium scores. Med Sci Sports Exerc. (2017) 49:2369–73. 10.1249/MSS.0000000000001373
    1. Laddu DR, Rana JS, Murillo R, Sorel ME, Quesenberry CPJr, Allen NB, et al. . 25-Year physical activity trajectories and development of subclinical coronary artery disease as measured by coronary artery calcium: the Coronary Artery Risk Development in Young Adults (CARDIA) study. Mayo Clin Proc. (2017) 92:1660–70. 10.1016/j.mayocp.2017.07.016
    1. Aengevaeren VL, Mosterd A, Braber TL, Prakken NHJ, Doevendans PA, Grobbee DE, et al. . Relationship between lifelong exercise volume and coronary atherosclerosis in athletes. Circulation (2017) 136:138–48. 10.1161/CIRCULATIONAHA.117.027834
    1. Merghani A, Maestrini V, Rosmini S, Cox AT, Dhutia H, Bastiaenan R, et al. . Prevalence of subclinical coronary artery disease in masters endurance athletes with a low atherosclerotic risk profile. Circulation (2017) 136:126–37. 10.1161/CIRCULATIONAHA.116.026964
    1. Howden EJ, Sarma S, Lawley JS, Opondo M, Cornwell W, Stoller D, et al. . Reversing the cardiac effects of sedentary aging in middle age-a randomized controlled trial: implications for heart failure prevention. Circulation (2018) 137:1549–60. 10.1161/CIRCULATIONAHA.117.030617
    1. Mora S, Cook N, Buring JE, Ridker PM, Lee IM. Physical activity and reduced risk of cardiovascular events: potential mediating mechanisms. Circulation (2007) 116:2110–8. 10.1161/CIRCULATIONAHA.107.729939
    1. Fernandez DM, Clemente JC, Giannarelli C. Physical activity, immune system, and the microbiome in cardiovascular disease. Front Physiol. (2018) 9:763. 10.3389/fphys.2018.00763
    1. Fiuza-Luces C, Santos-Lozano A, Joyner M, Carrera-Bastos P, Picazo O, Zugaza JL, et al. . Exercise benefits in cardiovascular disease: beyond attenuation of traditional risk factors. Nat Rev Cardiol. (2018). 10.1038/s41569-018-0065-1
    1. Boldyrev AA, Aldini G, Derave W. Physiology and pathophysiology of carnosine. Physiol Rev. (2013) 93:1803–45. 10.1152/physrev.00039.2012

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