Inflammatory biomarkers are unrelated to endothelial-mediated vasodilation in physically active young men
DOI:
https://doi.org/10.4100/jhse.2012.72.21Keywords:
Endothelial dysfunction, CRP, TNF-α, IL-6, Physical activityAbstract
Endothelial dysfunction has an important role in genesis of atherosclerosis and is depicted by a series of inflammatory and endothelial biomarkers. Shear stress arising from repeated episodes of increased blood flow with physical activity (PA) is a possible mechanism that improves vascular endothelial function. Our purpose was to examine whether inflammatory markers mediate the association between PA and endothelial function. Subjects were young, healthy men recruited according to recreational PA habits: high-active (n=21) vs. sedentary (n=17). Active subjects reported >45 min/day of moderate-vigorous physical activities, >4 days/week over 6 months, while sedentary subjects reported no recreational physical activity. Fasting serum samples were analyzed for C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Endothelial function was determined using flow-mediated dilation of the brachial artery induced by post ischemic reactive hyperemia. Hyperemia response was greater in the high-active than in sedentary men (30.2±8.2 vs. 24.3±5.2 mL/min/100mL; P<0.001). There were no differences between the groups with respect to CRP, TNF-α, or IL-6. Concentrations of these inflammatory biomarkers were unrelated to reactive hyperemia differences attributable to PA. Improved hyperemic response seen in young physically active subjects may be influenced by factors beyond the inflammatory factors, e.g., enhanced nitric oxide production. Physical activity was associated with an increased vascular function in young adults, although a diminished inflammatory state was no revealed. Additional research is needed to clarify the role of PA on cytokine indicators of inflammation and how this relates to endothelial function.Downloads
References
ALOMARI MA, SOLOMITO A, REYES R, KHALIL SM, WOOD RH, WELSCH MA. Measurements of vascular function using strain-gauge plethysmography: technical considerations, standardization, and physiological findings. Am J Physiol Heart Circ Physiol. 2004; 286:H99-H107. https://doi.org/10.1152/ajpheart.00529.2003
AMERICAN COLLEGE OF SPORTS MEDICINE. ACSM's guidelines for exercise testing and prescription (7th Ed.). New York: Lippincott Williams & Wilkins; 2006.
BENJAMIN EJ, LARSON MG, KEYES MJ, MITCHELL GF, VASAN RS, KEANEY JF, et al. 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
Bhagat K, Moss R, Collier J, Vallance P. Endothelial "stunning" following a brief exposure to endotoxin: a mechanism to link infection and infarction? Cardiovasc Res. 1996; 32:822-829.
BREVETTI G, SILVESTRO A, DI GIACOMO S, BUCUR R, DI DONATO A, SCHIANO V, et al. Endothelial dysfunction in peripheral arterial disease is related to increase in plasma markers of inflammation and severity of peripheral circulatory impairment but not to classic risk factors and atherosclerotic burden. J Vasc Surg. 2003; 38:374-379. https://doi.org/10.1016/S0741-5214(03)00124-1
BRUUNSGAARD H. Physical activity and modulation of systemic low-level inflammation. J Leukoc Biol. 2005; 78:819-835. https://doi.org/10.1189/jlb.0505247
DAKAK N, HUSAIN S, MULCAHY D, ANDREWS NP, PANZA JA, WACLAWIW M, ET AL. Contribution of nitric oxide to reactive hyperemia: impact of endothelial dysfunction. Hypertension. 1998; 32:9-15. https://doi.org/10.1161/01.HYP.32.1.9
DESOUZA CA, SHAPIRO LF, CLEVENGER CM, DINENNO FA, MONAHAN KD, TANAKA H, ET AL. Regular aerobic exercise prevents and restores age-related declines in endothelium-dependent vasodilation in healthy men. Circulation. 2000; 102:1351-1357. https://doi.org/10.1161/01.CIR.102.12.1351
FICHTLSCHERER S, ROSENBERGER G, WALTER DH, BREUER S, DIMMELER S, ZEIHER AM. ElevatedC-reactive protein levels and impaired endothelial vasoreactivity in patients with coronary artery disease. Circulation. 2000; 102:1000-1006. https://doi.org/10.1161/01.CIR.102.9.1000
Green D, Cheetham C, Mavaddat L, Watts K, Best M, Taylor R, et al. Effect of lower limb exercise on forearm vascular function: contribution of nitric oxide. Am J Physiol Heart Circ Physiol. 2002; 283:H899-907. https://doi.org/10.1152/ajpheart.00049.2002
HORNIG B, MAIER V, DREXLER H. Physical training improves endothelial function in patients with chronic heart failure. Circulation. 1996; 93:210-214. https://doi.org/10.1161/01.CIR.93.2.210
JARVISALO MJ, TOIKKA JO, VASANKARI T, MIKKOLA J, VIIKARI JS, HARTIALA JJ, et al. HMG CoA reductase inhibitors are related to improved systemic endothelial function in coronary artery disease. Atherosclerosis. 1999; 147:237-242. https://doi.org/10.1016/S0021-9150(99)00189-6
KASAPIS C, THOMPSON PD. The effects of physical activity on serum C-reactive protein and inflammatory markers: a systematic review. J Am Coll Cardiol. 2005; 45:1563-1569. https://doi.org/10.1016/j.jacc.2004.12.077
KATHIRESAN S, GONA P, LARSON MG, VITA JA, MITCHELL GF, TOFLER GH, et al. Cross-sectional relations of multiple biomarkers from distinct biological pathways to brachial artery endothelial function. Circulation. 2006; 113:938-945. https://doi.org/10.1161/CIRCULATIONAHA.105.580233
KELLY AS, STEINBERGER J, OLSON TP, DENGEL DR. In the absence of weight loss, exercise training does not improve adipokines or oxidative stress in overweight children. Metabolism. 2007; 56:1005-1009. https://doi.org/10.1016/j.metabol.2007.03.009
MAKIMATTILA S, LIU ML, VAKKILAINEN J, SCHLENZKA A, LAHDENPERA S, SYVANNE M, et al. Impaired endothelium-dependent vasodilation in type 2 diabetes. Relation to LDL size, oxidized LDL, and antioxidants. Diabetes Care. 1999; 22:973-981. https://doi.org/10.2337/diacare.22.6.973
NIEBAUER J, MAXWELL AJ, LIN PS, TSAO PS, KOSEK J, BERNSTEIN D, et al. Impaired aerobic capacity in hypercholesterolemic mice: partial reversal by exercise training. Am J Physiol. 1999; 276:H1346-1354. https://doi.org/10.1152/ajpheart.1999.276.4.H1346
PALMIERI EA, PALMIERI V, INNELLI P, AREZZI E, FERRARA LA, CELENTANO A, et al. Aerobic exercise performance correlates with post-ischemic flow-mediated dilation of the brachial artery in young healthy men. Eur J Appl Physiol. 2005; 94:113-117. https://doi.org/10.1007/s00421-004-1285-0
PANAGIOTAKOS DB, PITSAVOS C, CHRYSOHOOU C, KAVOURAS S, STEFANADIS C. The associations between leisure-time physical activity and inflammatory and coagulation markers related to cardiovascular disease: the ATTICA Study. Prev Med. 2005; 40:432-437. https://doi.org/10.1016/j.ypmed.2004.07.010
PITSAVOS C, CHRYSOHOOU C, PANAGIOTAKOS DB, SKOUMAS J, ZEIMBEKIS A, KOKKINOS P, et al. Association of leisure-time physical activity on inflammation markers (C-reactive protein, white cell blood count, serum amyloid A, and fibrinogen) in healthy subjects (from the ATTICA study). Am J Cardiol. 2003; 91:368-370. https://doi.org/10.1016/S0002-9149(02)03175-2
RIBEIRO F, ALVES AJ, DUARTE JA, OLIVEIRA J. Is exercise training an effective therapy targeting endothelial dysfunction and vascular wall inflammation? Int J Cardiol. 2010; 141:214-221. https://doi.org/10.1016/j.ijcard.2009.09.548
RINDER MR, SPINA RJ, EHSANI AA. Enhanced endothelium-dependent vasodilation in older endurance-trained men. J Appl Physiol. 2000; 88:761-766. https://doi.org/10.1152/jappl.2000.88.2.761
ROSS R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993; 362:801-809. https://doi.org/10.1038/362801a0
SCHROEDER S, ENDERLE MD, OSSEN R, MEISNER C, BAUMBACH A, PFOHL M, et al. Noninvasive determination of endothelium-mediated vasodilation as a screening test for coronary artery disease: pilot study to assess the predictive value in comparison with angina pectoris, exercise electrocardiography, and myocardial perfusion imaging. Am Heart J. 1999; 138:731-739. https://doi.org/10.1016/S0002-8703(99)70189-4
STEINER S, NIESSNER A, ZIEGLER S, RICHTER B, SEIDINGER D, PLEINER J, et al. Endurance training increases the number of endothelial progenitor cells in patients with cardiovascular risk and coronary artery disease. Atherosclerosis. 2005; 181:305-310. https://doi.org/10.1016/j.atherosclerosis.2005.01.006
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; 76:2241-2247. https://doi.org/10.1152/jappl.1994.76.5.2241
TADDEI S, VIRDIS A, MATTEI P, GHIADONI L, GENNARI A, FASOLO CB, et al. Aging and endothelial function in normotensive subjects and patients with essential hypertension. Circulation. 1995; 91:1981-1987. https://doi.org/10.1161/01.CIR.91.7.1981
THOMAS NE, BAKER JS, GRAHAM MR, COOPER SM, DAVIES B. C-reactive protein in schoolchildren and its relation to adiposity, physical activity, aerobic fitness and habitual diet. Br J Sports Med. 2008; 42:357-360. https://doi.org/10.1136/bjsm.2007.043604
TINKEN TM, THIJSSEN DH, HOPKINS N, DAWSON EA, CABLE NT, GREEN DJ. Shear stress mediates endothelial adaptations to exercise training in humans. Hypertension. 2010; 55:312-318. https://doi.org/10.1161/HYPERTENSIONAHA.109.146282
WIDLANSKY ME, GOKCE N, KEANEY JF, VITA JA. The clinical implications of endothelial dysfunction. J Am Coll Cardiol. 2003; 42:1149-1160. https://doi.org/10.1016/S0735-1097(03)00994-X
Downloads
Statistics
Published
How to Cite
Issue
Section
License
Each author warrants that his or her submission to the Work is original and that he or she has full power to enter into this agreement. Neither this Work nor a similar work has been published elsewhere in any language nor shall be submitted for publication elsewhere while under consideration by JHSE. Each author also accepts that the JHSE will not be held legally responsible for any claims of compensation.
Authors wishing to include figures or text passages that have already been published elsewhere are required to obtain permission from the copyright holder(s) and to include evidence that such permission has been granted when submitting their papers. Any material received without such evidence will be assumed to originate from the authors.
Please include at the end of the acknowledgements a declaration that the experiments comply with the current laws of the country in which they were performed. The editors reserve the right to reject manuscripts that do not comply with the abovementioned requirements. The author(s) will be held responsible for false statements or failure to fulfill the above-mentioned requirements.
This title is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International license (CC BY-NC-ND 4.0).
You are free to share, copy and redistribute the material in any medium or format. The licensor cannot revoke these freedoms as long as you follow the license terms under the following terms:
Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
NonCommercial — You may not use the material for commercial purposes.
NoDerivatives — If you remix, transform, or build upon the material, you may not distribute the modified material.
No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
Notices:
You do not have to comply with the license for elements of the material in the public domain or where your use is permitted by an applicable exception or limitation.
No warranties are given. The license may not give you all of the permissions necessary for your intended use. For example, other rights such as publicity, privacy, or moral rights may limit how you use the material.
Transfer of Copyright
In consideration of JHSE’s publication of the Work, the authors hereby transfer, assign, and otherwise convey all copyright ownership worldwide, in all languages, and in all forms of media now or hereafter known, including electronic media such as CD-ROM, Internet, and Intranet, to JHSE. If JHSE should decide for any reason not to publish an author’s submission to the Work, JHSE shall give prompt notice of its decision to the corresponding author, this agreement shall terminate, and neither the author nor JHSE shall be under any further liability or obligation.
Each author certifies that he or she has no commercial associations (e.g., consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article, except as disclosed on a separate attachment. All funding sources supporting the Work and all institutional or corporate affiliations of the authors are acknowledged in a footnote in the Work.
Each author certifies that his or her institution has approved the protocol for any investigation involving humans or animals and that all experimentation was conducted in conformity with ethical and humane principles of research.
Competing Interests
Biomedical journals typically require authors and reviewers to declare if they have any competing interests with regard to their research.
JHSE require authors to agree to Copyright Notice as part of the submission process.
