Promena biomarkera oksidativnog stresa i funkcije endotela posle šestonedeljnog aerobnog fizičkog treninga kod bolesnika sa stabilnom ishemijskom bolesti srca
Sažetak
Uvod/Cilj. Redovna fizička aktivnost u sklopu kardiovaskularne rehabiltacije popravlja endotelnu funkciju, redukuje kardiovaskularni mortalitet i anginozne tegobe bolesnika sa kardiovaskularnim oboljenjem. U radu su analizirane promene parametara oksidativnog stresa i endotelne funkcije nakon sprovedenog redovnog aerobnog fizičkog treninga tokom šest nedelja kod bolesnika sa stabilnom formom koronarne bolesti (KB) uključenih u program kardiovaskularne rehabilitacije. Metode. Analizirano je 35 uzastopnih bolesnika sa stabilnom formom KB, uključenih u program kardiovaskularne rehabilitacije sa redovnom aerobnom fizičkom aktivnošću tokom šest nedelja, zajedno sa 37 kontrolnih bolesnika sa KB, uparenih prema polu i starosti, sa sedentarnim načinom života. Anamnestički podaci o komorbiditetima, faktorima rizika od kardiovaskularnih bolesti, primenjenoj terapiji, klinički podaci o antropometrijskim i kardiovaskularnim parametrima kao i laboratorijske analize: adhezioni molekuli, derivati oksidativne modifikacije proteina (RCD), derivati lipidne peroksidacije malondialdehid (MDA) i azot monoksid (NO) određivani su na početku i nakon šest nedelja aerobnog treninga. Trening se sastojao od 45 minuta kontinuirane fizičke aktivnosti (do 80% maksimalne srčane frekvencije), tri puta nedeljno. Rezultati. Karakteristike grupa na početku studije bile su slične u pogledu polne i starosne strukture, kao i prisustva faktora rizika od kardiovaskularnih bolesti. Redovna aerobna fizička aktivnost dovodila je do značajne redukcije indeksa telesne mase, krvnog pritiska, srčane frekvencije, koncentracije triglicerida, RCD (1,27 ± 0,48 µmol/g proteins naspram 1,04 ± 0,22 µmol/g proteins), sVCAM-1 [100.4 (IQR) (78,4–118,3) ng/mL naspram 80,0 IQR (68,5–97,2 µmol/g proteins)] i povećanja NO (64,72 ± 16,06 µmol/g proteins prema 74,38 ± 18,57) i HDL holesterola (p < 0,05), što nije registrovano u sedentarnoj kontroli: RCD (1,16 ± 0,25 naspram 1,12 ± 0,14), sVCAM-1 [92,2 IQR (73,6–106,8) naspram 91,3 IQR(73,0–105,3)] i NO (68,5 ± 17,9 naspram 65,7 ± 19,6). Serumske vrednosti intracelularnog adhezionog molekula sICAM-1 su startno bile niže u grupi sa primenjenim treningom bez značajne promene tokom praćenja [80,74 IQR (54,92–97,3) vs 80,36 IQR (68,1–95,3)] u odnosu na kontrolnu grupu [86,35 IQR (57,32–95,8)] vs 84,65 IQR (55,67–93,8). U grupi sa fizičkim treningom vrednosti sVCAM-1 i RCD su bile značajno niže a NO više na kraju studije u poređenju sa kontrolnom grupom. Zaključak. Redovan fizički trening indukuje smanjenje intenziteta oksidativnog stresa i ćelijskih adhezionih molekula uz porast bioraspoloživog NO i povoljne promene HDL holesterola i triglicerida.
Reference
Yoshinaga K, Beanlands RS, Dekemp RA, Lortie M, Morin J, Aung M, et al. Effect of exercise training on myocardial blood flow in patients with stable coronary artery disease. Am Heart J 2006; 151(6): 1324.e11−8.
Hambrecht R, Adams V, Erbs S, Linke A, Kränkel N, Shu Y, et al. Regular physical activity improves endothelial function in pa-tients with coronary artery disease by increasing phosphoryla-tion of endothelial nitric oxide synthase. Circulation 2003; 107(25): 3152−8.
Leon AS, Franklin BA, Costa F, Balady GJ, Berra KA, Stewart KJ, et al. Cardiac rehabilitation and secondary prevention of coro-nary heart disease: An American Heart Association scientific statement from the Council on Clinical Cardiology (Subcom-mittee on Exercise, Cardiac Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabo-lism (Subcommittee on Physical Activity), in collaboration with the American association of Cardiovascular and Pulmonary Rehabilitation Circulation 2005; 111(3): 369−76.
Myers J, Prakash M, Froelicher V, Do D, Partington S, Atwood EJ. Exercise capacity and mortality among men referred for exer-cise testing. N Engl J Med 2002; 346(11): 793−801.
Brandes RP, Kreuzer J. Vascular NADPH oxidases: Molecular mechanisms of activation. Cardiovasc Res 2005; 65(1): 16−27.
Campos JC, Gomes KM, Ferreira JC. Impact of exercise training on redox signaling in cardiovascular diseases. Food Chem Toxicol 2013; 62: 107−19.
Lavie CJ, Thomas RJ, Squires RW, Allison TG, Milani RV. Exercise training and cardiac rehabilitation in primary and secondary prevention of coronary heart disease. Mayo Clin Proc 2009; 84(4): 373−83.
Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F, et al. Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. Eur Heart J 2006; 27(11): 1341−81.
Pickering TG, Hall JE, Appel LJ, Falkner BE, Graves J, Hill MN, et al. Recommendations for blood pressure measurement in humans and experimental animals: Part 1: Blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Circulation 2005; 111(5): 697−716.
Navarro-Gonzálvez JA, García-Benayas C, Arenas J. Semiautomated measurement of nitrate in biological fluids. Clin Chem 1998; 44(3): 679–81.
Andreeva LI, Kozhemiakin LA, Kishkun AA. Modification of the method of determining lipid peroxidation in a test using thio-barbituric acid. Lab Delo 1988; 11: 41−3. (Russian)
Levine RL, Williams JA, Stadtman ER, Shacter E. Carbonyl assays for determination of oxidatively modified proteins. Methods Enzymol 1994; 233: 346−57.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193(1): 265−75.
Whelton SP, Chin A, Xin X, He J. Effect of aerobic exercise on blood pressure: A meta-analysis of randomized, controlled tri-als. Ann Intern Med 2002; 136(7): 493−503.
Nemoto K, Gen-Hirokazu , Masuki S, Okazaki K, Nose H. Effects of high-intensity interval walking training on physical fitness and blood pressure in middle-aged and older people. Mayo Clin Proc 2007; 82(7): 803−11.
Anton MM, Cortez-Cooper MY, DeVan AE, Neidre DB, Cook JN, Tanaka H. Cigarette smoking, regular exercise, and peripheral blood flow. Atherosclerosis 2006; 185(1): 201−5.
Pal S, Radavelli-Bagatini S, Ho S. Potential benefits of exercise on blood pressure and vascular function. J Am Soc Hypertens 2013; 7(6): 494−506.
Wilkinson IB, Prasad K, Hall IR, Thomas A, MacCallum H, Webb DJ, et al. Increased central pulse pressure and augmentation index in subjects with hypercholesterolemia. J Am Coll Cardiol 2002; 39(6): 1005−11.
Berent R, von Duvillard SP, Crouse SF, Auer J, Green JS, Sinzinger H, et al. Short-term residential cardiac rehabilitation reduces B-type natriuretic peptide. Eur J Cardiovasc Prev Rehabil 2009; 16(5): 603−8.
Volaklis KA, Spassis AT, Tokmakidis SP. Land versus water ex-ercise in patients with coronary artery disease: Effects on body composition, blood lipids, and physical fitness. Am Heart J 2007; 154(3): 560.e1−6.
Chow CK, Jolly S, Rao-Melacini P, Fox KA, Anand SS, Yusuf S. Association of diet, exercise, and smoking modification with risk of early cardiovascular events after acute coronary syn-dromes. Circulation 2010; 121(6): 750−8.
Clark AM, Hartling L, Vandermeer B, McAlister FA. Meta-analysis: Secondary prevention programs for patients with coronary artery disease. Ann Intern Med 2005; 143(9): 659−72.
Blankenberg S, Barbaux S, Tiret L. Adhesion molecules and ath-erosclerosis. Atherosclerosis 2003; 170(2): 191−203.
Lim S, Min S, Park H, Park J, Park J. Effects of a healthy life exercise program on arteriosclerosis adhesion molecules in el-derly obese women. J Phys Ther Sci 2015; 27(5): 1529−32.
Peter K, Weirich U, Nordt TK, Ruef J, Bode C. Soluble vascular cell adhesion molecule-1 (VCAM-1) as potential marker of athero-sclerosis. Thromb Haemost 1999; 89(Suppl 1): 38−43.
Aksoy S, Findikoglu G, Ardic F, Rota S, Dursunoglu D. Effect of 10-Week Supervised Moderate-Intensity Intermittent vs. Con-tinuous Aerobic Exercise Programs on Vascular Adhesion Molecules in Patients with Heart Failure. Am J Phys Med Re-habil 2015; 94 (10 Suppl 1):): 898−911.
Lim S, Min S, Kwon Y, Park S, Park H. Effects of intermittent exercise on biomarkers of cardiovascular risk in night shift workers. Atherosclerosis 2015; 242(1): 186−90.
Palmefors H, DuttaRoy S, Rundqvist B, Börjesson M. The effect of physical activity or exercise on key biomarkers in atherosclero-sis: A systematic review. Atherosclerosis 2014; 235(1): 150−61.
Tönjes A, Scholz M, Fasshauer M, Kratzsch J, Rassoul F, Stumvoll M, et al. Beneficial effects of a 4-week exercise program on plasma concentrations of adhesion molecules. Diabetes Care 2007; 30(3): e1.
Ziccardi P, Nappo F, Giugliano G, Esposito K, Marfella R, Cioffi M, et al. Reduction of inflammatory cytokine concentrations and improvement of endothelial functions in obese women after weight loss over one year. Circulation 2002; 105(7): 804−9.
Beer VJ, Bender SB, Taverne YJ, Gao F, Duncker DJ, Laughlin HM, et al. Exercise limits the production of endothelin in the coro-nary vasculature. Am J Physiol Heart Circ Physiol 2011; 300(5): H1950−9.
Luk T, Dai Y, Siu C, Yiu K, Chan H, Lee SW, et al. Effect of exercise training on vascular endothelial function in patients with stable coronary artery disease: a randomized controlled trial. Eur J Prev Cardiol 2012; 19(4): 830−9.
Murphy E, Kohr M, Sun J, Nguyen T, Steenbergen C. S-nitrosylation: a radical way to protect the heart. J Mol Cell Cardiol 2012; 52(3): 568−77.
Sun J, Kohr MJ, Nguyen T, Aponte AM, Connelly PS, Esfahani SG, et al. Disruption of caveolae blocks ischemic preconditioning-mediated S-nitrosylation of mitochondrial proteins. Antioxid. Redox Signal 2012; 16(1): 45−56.