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Interaction of genetic background and exercise training intensity on endothelial function in mouse aorta

  • Kim, Seung Kyum (Department of Sports Science, Seoul National University of Science and Technology) ;
  • Avila, Joshua J. (Department of Health and Kinesiology, Texas A&M University) ;
  • Massett, Michael P. (Department of Health and Kinesiology, Texas A&M University)
  • 투고 : 2019.07.17
  • 심사 : 2019.11.07
  • 발행 : 2020.01.01

초록

The purpose of this study was to characterize the genetic contribution to endothelial adaptation to exercise training. Vasoreactivity was assessed in aortas from four inbred mouse strains (129S1, B6, NON, and SJL) after 4 weeks of moderate intensity continuous exercise training (MOD), high intensity interval training (HIT) or in sedentary controls (SED). Intrinsic variations in endothelium-dependent vasorelaxation (EDR) to acetylcholine (ACh) as well as vasocontractile responses were observed across SED groups. For responses to exercise training, there was a significant interaction between mouse strain and training intensity on EDR. Exercise training had no effect on EDR in aortas from 129S1 and B6 mice. In NON, EDR was improved in aortas from MOD and HIT compared with respective SED, accompanied by diminished responses to PE in those groups. Interestingly, EDR was impaired in aorta from SJL HIT compared with SED. The transcriptional activation of endothelial genes was also influenced by the interaction between mouse strain and training intensity. The number of genes altered by HIT was greater than MOD, and there was little overlap between genes altered by HIT and MOD. HIT was associated with gene pathways for inflammatory responses. NON MOD genes showed enrichment for vessel growth pathways. These findings indicate that exercise training has non-uniform effects on endothelial function and transcriptional activation of endothelial genes depending on the interaction between genetic background and training intensity.

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참고문헌

  1. Mitchell JA, Ali F, Bailey L, Moreno L, Harrington LS. Role of nitric oxide and prostacyclin as vasoactive hormones released by the endothelium. Exp Physiol. 2008;93:141-147. https://doi.org/10.1113/expphysiol.2007.038588
  2. Delp MD, McAllister RM, Laughlin MH. Exercise training alters endothelium-dependent vasoreactivity of rat abdominal aorta. J Appl Physiol (1985). 1993;75:1354-1363. https://doi.org/10.1152/jappl.1993.75.3.1354
  3. Kemi OJ, Haram PM, Loennechen JP, Osnes JB, Skomedal T, Wisloff U, Ellingsen O. Moderate vs. high exercise intensity: differential effects on aerobic fitness,cardiomyocyte contractility, and endothelial function. Cardiovasc Res. 2005;67:161-172. https://doi.org/10.1016/j.cardiores.2005.03.010
  4. Higashi Y, Sasaki S, Kurisu S, Yoshimizu A, Sasaki N, Matsuura H, Kajiyama G, Oshima T. Regular aerobic exercise augments endothelium-dependent vascular relaxation in normotensive as well as hypertensive subjects: role of endothelium-derived nitric oxide. Circulation. 1999;100:1194-1202. https://doi.org/10.1161/01.CIR.100.11.1194
  5. Jasperse JL, Laughlin MH. Endothelial function and exercise training: evidence from studies using animal models. Med Sci Sports Exerc. 2006;38:445-454. https://doi.org/10.1249/01.mss.0000191187.24525.f2
  6. Sessa WC, Pritchard K, Seyedi N, Wang J, Hintze TH. Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitric oxide synthase gene expression. Circ Res. 1994;74:349-353. https://doi.org/10.1161/01.RES.74.2.349
  7. Rush JW, Laughlin MH, Woodman CR, Price EM. SOD-1 expression in pig coronary arterioles is increased by exercise training. Am J Physiol Heart Circ Physiol. 2000;279:H2068-H2076. https://doi.org/10.1152/ajpheart.2000.279.5.H2068
  8. Muller JM, Myers PR, Laughlin MH. Vasodilator responses of coronary resistance arteries of exercise-trained pigs. Circulation. 1994;89:2308-2314. https://doi.org/10.1161/01.CIR.89.5.2308
  9. Green DJ, Eijsvogels T, Bouts YM, Maiorana AJ, Naylor LH, Scholten RR, Spaanderman ME, Pugh CJ, Sprung VS, Schreuder T, Jones H, Cable T, Hopman MT, Thijssen DH. Exercise training and artery function in humans: nonresponse and its relationship to cardiovascular risk factors. J Appl Physiol (1985). 2014;117:345-352. https://doi.org/10.1152/japplphysiol.00354.2014
  10. Ryan MJ, Didion SP, Davis DR, Faraci FM, Sigmund CD. Endothelial dysfunction and blood pressure variability in selected inbred mouse strains. Arterioscler Thromb Vasc Biol. 2002;22:42-48. https://doi.org/10.1161/hq0102.101098
  11. Chen C, Korshunov VA, Massett MP, Yan C, Berk BC. Impaired vasorelaxation in inbred mice is associated with alterations in both nitric oxide and super oxide pathways. J Vasc Res. 2007;44:504-512. https://doi.org/10.1159/000106751
  12. Kim SK, Avila JJ, Massett MP. Strain survey and genetic analysis of vasoreactivity in mouse aorta. Physiol Genomics. 2016;48:861-873. https://doi.org/10.1152/physiolgenomics.00054.2016
  13. Benjamin EJ, Larson MG, Keyes MJ, Mitchell GF, Vasan RS, Keaney JF Jr, Lehman BT, Fan S, Osypiuk E, Vita JA. Clinical correlates and heritability of flow-mediated dilation in the community: the Framingham Heart Study. Circulation. 2004;109:613-619. https://doi.org/10.1161/01.CIR.0000112565.60887.1E
  14. Zhao J, Cheema FA, Reddy U, Bremner JD, Su S, Goldberg J, Snieder H, Vaccarino V. Heritability of flow-mediated dilation: a twin study. J Thromb Haemost. 2007;5:2386-2392. https://doi.org/10.1111/j.1538-7836.2007.02760.x
  15. Suzuki K, Juo SH, Rundek T, Boden-Albala B, Disla N, Liu R, Park N, Di Tullio MR, Sacco RL, Homma S. Genetic contribution to brachial artery flow-mediated dilation: the Northern Manhattan Family Study. Atherosclerosis. 2008;197:212-216. https://doi.org/10.1016/j.atherosclerosis.2007.03.023
  16. Kim SK, Massett MP. Genetic regulation of endothelial vasomotor function. Front Physiol. 2016;7:571.
  17. Hopkins N, Stratton G, Maia J, Tinken TM, Graves LE, Cable TN, Green DJ. Heritability of arterial function, fitness, and physical activity in youth: a study of monozygotic and dizygotic twins. J Pediatr. 2010;157:943-948. https://doi.org/10.1016/j.jpeds.2010.06.005
  18. Hopkins ND, Stratton G, Cable NT, Tinken TM, Graves LE, Green DJ. Impact of exercise training on endothelial function and body composition in young people: a study of mono- and di-zygotic twins. Eur J Appl Physiol. 2012;112:421-427. https://doi.org/10.1007/s00421-011-1993-1
  19. Swain DP, Franklin BA. Comparison of cardioprotective benefits of vigorous versus moderate intensity aerobic exercise. Am J Cardiol. 2006;97:141-147. https://doi.org/10.1016/j.amjcard.2005.07.130
  20. Helgerud J, Hoydal K, Wang E, Karlsen T, Berg P, Bjerkaas M, Simonsen T, Helgesen C, Hjorth N, Bach R, Hoff J. Aerobic highintensity intervals improve VO2max more than moderate training. Med Sci Sports Exerc. 2007;39:665-671. https://doi.org/10.1249/mss.0b013e3180304570
  21. Hoydal MA, Wisloff U, Kemi OJ, Ellingsen O. Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training. Eur J Cardiovasc Prev Rehabil. 2007;14:753-760. https://doi.org/10.1097/HJR.0b013e3281eacef1
  22. Chung E, Diffee GM. Moderate intensity, but not high intensity, treadmill exercise training alters power output properties in myocardium from aged rats. J Gerontol A Biol Sci Med Sci. 2012;67:1178-1187. https://doi.org/10.1093/gerona/gls146
  23. Hafstad AD, Lund J, Hadler-Olsen E, Höper AC, Larsen TS, Aasum E. High- and moderate-intensity training normalizes ventricular function and mechanoenergetics in mice with diet-induced obesity. Diabetes. 2013;62:2287-2294. https://doi.org/10.2337/db12-1580
  24. Rognmo O, Moholdt T, Bakken H, Hole T, Molstad P, Myhr NE, Grimsmo J, Wisloff U. Cardiovascular risk of high- versus moderate-intensity aerobic exercise in coronary heart disease patients. Circulation. 2012;126:1436-1440. https://doi.org/10.1161/CIRCULATIONAHA.112.123117
  25. Bergholm R, Makimattila S, Valkonen M, Liu ML, Lahdenpera S, Taskinen MR, Sovijarvi A, Malmberg P, Yki-Jarvinen H. Intense physical training decreases circulating antioxidants and endothelium-dependent vasodilatation in vivo. Atherosclerosis. 1999;145:341-349. https://doi.org/10.1016/S0021-9150(99)00089-1
  26. Iemitsu M, Miyauchi T, Maeda S, Yuki K, Kobayashi T, Kumagai Y, Shimojo N, Yamaguchi I, Matsuda M. Intense exercise causes decrease in expression of both endothelial NO synthase and tissue NOx level in hearts. Am J Physiol Regul Integr Comp Physiol. 2000;279:R951-R959. https://doi.org/10.1152/ajpregu.2000.279.3.R951
  27. Goto C, Higashi Y, Kimura M, Noma K, Hara K, Nakagawa K, Kawamura M, Chayama K, Yoshizumi M, Nara I. Effect of different intensities of exercise on endothelium-dependent vasodilation in humans: role of endothelium-dependent nitric oxide and oxidative stress. Circulation. 2003;108:530-535. https://doi.org/10.1161/01.CIR.0000080893.55729.28
  28. Benito B, Gay-Jordi G, Serrano-Mollar A, Guasch E, Shi Y, Tardif JC, Brugada J, Nattel S, Mont L. Cardiac arrhythmogenic remodeling in a rat model of long-term intensive exercise training. Circulation. 2011;123:13-22. https://doi.org/10.1161/CIRCULATIONAHA.110.938282
  29. Haram PM, Kemi OJ, Lee SJ, Bendheim MO, Al-Share QY, Waldum HL, Gilligan LJ, Koch LG, Britton SL, Najjar SM, Wisloff U. Aerobic interval training vs. continuous moderate exercise in the metabolic syndrome of rats artificially selected for low aerobic capacity. Cardiovasc Res. 2009;81:723-732. https://doi.org/10.1093/cvr/cvn332
  30. Murias JM, Dey A, Campos OA, Estaki M, Hall KE, Melling CW, Noble EG. High-intensity endurance training results in faster vesselspecific rate of vasorelaxation in type 1 diabetic rats. PLoS One. 2013;8:e59678. https://doi.org/10.1371/journal.pone.0059678
  31. Tjonna AE, Lee SJ, Rognmo O, Stolen TO, Bye A, Haram PM, Loennechen JP, Al-Share QY, Skogvoll E, Slordahl SA, Kemi OJ, Najjar SM, Wisloff U. Aerobic interval training versus continuous moderate exercise as a treatment for the metabolic syndrome: a pilot study. Circulation. 2008;118:346-354. https://doi.org/10.1161/CIRCULATIONAHA.108.772822
  32. Rakobowchuk M, Tanguay S, Burgomaster KA, Howarth KR, Gibala MJ, MacDonald MJ. Sprint interval and traditional endurance training induce similar improvements in peripheral arterial stiffness and flow-mediated dilation in healthy humans. Am J Physiol Regul Integr Comp Physiol. 2008;295:R236-R242. https://doi.org/10.1152/ajpregu.00069.2008
  33. Petkov PM, Ding Y, Cassell MA, Zhang W, Wagner G, Sargent EE, Asquith S, Crew V, Johnson KA, Robinson P, Scott VE, Wiles MV. An efficient SNP system for mouse genome scanning and elucidating strain relationships. Genome Res. 2004;14:1806-1811. https://doi.org/10.1101/gr.2825804
  34. Avila JJ, Kim SK, Massett MP. Differences in exercise capacity and responses to training in 24 inbred mouse strains. Front Physiol. 2017;8:974. https://doi.org/10.3389/fphys.2017.00974
  35. Massett MP, Avila JJ, Kim SK. Exercise capacity and response to training quantitative trait loci in a NZW X 129S1 intercross and combined cross analysis of inbred mouse strains. PLoS One. 2015;10:e0145741. https://doi.org/10.1371/journal.pone.0145741
  36. Spinazzi M, Casarin A, Pertegato V, Salviati L, Angelini C. Assessment of mitochondrial respiratory chain enzymatic activities on tissues and cultured cells. Nat Protoc. 2012;7:1235-1246. https://doi.org/10.1038/nprot.2012.058
  37. Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res. 2000;87:840-844. https://doi.org/10.1161/01.RES.87.10.840
  38. Seals DR. Edward F. Adolph distinguished lecture: the remarkable anti-aging effects of aerobic exercise on systemic arteries. J Appl Physiol (1985). 2014;117:425-439. https://doi.org/10.1152/japplphysiol.00362.2014
  39. Prochazka M, Serreze DV, Worthen SM, Leiter EH. Genetic control of diabetogenesis in NOD/Lt mice. Development and analysis of congenic stocks. Diabetes. 1989;38:1446-1455. https://doi.org/10.2337/diab.38.11.1446
  40. Svenson KL, Von Smith R, Magnani PA, Suetin HR, Paigen B, Naggert JK, Li R, Churchill GA, Peters LL. Multiple trait measurements in 43 inbred mouse strains capture the phenotypic diversity characteristic of human populations. J Appl Physiol (1985). 2007;102:2369-2378. https://doi.org/10.1152/japplphysiol.01077.2006
  41. Hoshino J, Sakamaki T, Nakamura T, Kobayashi M, Kato M, Sakamoto H, Kurashina T, Yagi A, Sato K, Ono Z. Exaggerated vascular response due to endothelial dysfunction and role of the reninangiotensin system at early stage of renal hypertension in rats. Circ Res. 1994;74:130-138. https://doi.org/10.1161/01.RES.74.1.130
  42. Durand MJ, Gutterman DD. Exercise and vascular function: how much is too much? Can J Physiol Pharmacol. 2014;92:551-557. https://doi.org/10.1139/cjpp-2013-0486
  43. Delp MD, Laughlin MH. Time course of enhanced endotheliummediated dilation in aorta of trained rats. Med Sci Sports Exerc. 1997;29:1454-1461. https://doi.org/10.1097/00005768-199711000-00011
  44. Green DJ, Cable NT, Fox C, Rankin JM, Taylor RR. Modification of forearm resistance vessels by exercise training in young men. J Appl Physiol (1985). 1994;77:1829-1833. https://doi.org/10.1152/jappl.1994.77.4.1829
  45. Padilla J, Newcomer SC, Simmons GH, Kreutzer KV, Laughlin MH. Long-term exercise training does not alter brachial and femoral artery vasomotor function and endothelial phenotype in healthy pigs. Am J Physiol Heart Circ Physiol. 2010;299:H379-H385. https://doi.org/10.1152/ajpheart.00294.2010
  46. Trott DW, Gunduz F, Laughlin MH, Woodman CR. Exercise training reverses age-related decrements in endothelium-dependent dilation in skeletal muscle feed arteries. J Appl Physiol (1985). 2009;106:1925-1934. https://doi.org/10.1152/japplphysiol.91232.2008
  47. Johnson LR, Laughlin MH. Chronic exercise training does not alter pulmonary vasorelaxation in normal pigs. J Appl Physiol (1985). 2000;88:2008-2014. https://doi.org/10.1152/jappl.2000.88.6.2008
  48. Batacan RB Jr, Duncan MJ, Dalbo VJ, Connolly KJ, Fenning AS. Light-intensity and high-intensity interval training improve cardiometabolic health in rats. Appl Physiol Nutr Metab. 2016;41:945-952. https://doi.org/10.1139/apnm-2016-0037
  49. Molmen-Hansen HE, Stolen T, Tjonna AE, Aamot IL, Ekeberg IS, Tyldum GA, Wisloff U, Ingul CB, Stoylen A. Aerobic interval training reduces blood pressure and improves myocardial function in hypertensive patients. Eur J Prev Cardiol. 2012;19:151-160. https://doi.org/10.1177/1741826711400512
  50. Wang JS. Intense exercise increases shear-induced platelet aggregation in men through enhancement of von Willbrand factor binding, glycoprotein IIb/IIIa activation, and P-selectin expression on platelets. Eur J Appl Physiol. 2004;91:741-747. https://doi.org/10.1007/s00421-004-1050-4
  51. Pereira BC, Filho LA, Alves GF, Pauli JR, Ropelle ER, Souza CT, Cintra DE, Saad MJ, Silva AS. A new overtraining protocol for mice based on downhill running sessions. Clin Exp Pharmacol Physiol. 2012;39:793-798. https://doi.org/10.1111/j.1440-1681.2012.05728.x
  52. Padilla J, Jenkins NT, Thorne PK, Martin JS, Rector RS, Davis JW, Laughlin MH. Transcriptome-wide RNA sequencing analysis of rat skeletal muscle feed arteries. II. Impact of exercise training in obesity. J Appl Physiol (1985). 2014;116:1033-1047. https://doi.org/10.1152/japplphysiol.01234.2013
  53. Padilla J, Simmons GH, Davis JW, Whyte JJ, Zderic TW, Hamilton MT, Bowles DK, Laughlin MH. Impact of exercise training on endothelial transcriptional profiles in healthy swine: a genome-wide microarray analysis. Am J Physiol Heart Circ Physiol. 2011;301:H555-H564. https://doi.org/10.1152/ajpheart.00065.2011
  54. Palmefors H, DuttaRoy S, Rundqvist B, Borjesson M. The effect of physical activity or exercise on key biomarkers in atherosclerosis--a systematic review. Atherosclerosis. 2014;235:150-161. https://doi.org/10.1016/j.atherosclerosis.2014.04.026
  55. Prior BM, Lloyd PG, Yang HT, Terjung RL. Exercise-induced vascular remodeling. Exerc Sport Sci Rev. 2003;31:26-33. https://doi.org/10.1097/00003677-200301000-00006
  56. Ratkevicius A, Carroll AM, Kilikevicius A, Venckunas T, McDermott KT, Gray SR, Wackerhage H, Lionikas A. H55N polymorphism as a likely cause of variation in citrate synthase activity of mouse skeletal muscle. Physiol Genomics. 2010;42A:96-102. https://doi.org/10.1152/physiolgenomics.00066.2010
  57. Laughlin MH, Welshons WV, Sturek M, Rush JW, Turk JR, Taylor JA, Judy BM, Henderson KK, Ganjam VK. Gender, exercise training, and eNOS expression in porcine skeletal muscle arteries. J Appl Physiol (1985). 2003;95:250-264. https://doi.org/10.1152/japplphysiol.00061.2003
  58. Laughlin MH, Schrage WG, McAllister RM, Garverick HA, Jones AW. Interaction of gender and exercise training: vasomotor reactivity of porcine skeletal muscle arteries. J Appl Physiol (1985). 2001;90:216-227. https://doi.org/10.1152/jappl.2001.90.1.216

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