Vascular Dysfunction and Chronic Obstructive Pulmonary Disease: The Role of Redox Balance

Stephen J Ives, Ryan A. Harris, Melissa A H Witman, Melissa A H Fjeldstad, Ryan S Garten, John McDaniel, D Walter Wray, Russell S Richardson

    Research output: Contribution to journalArticle

    46 Citations (Scopus)

    Abstract

    Chronic obstructive pulmonary disease (COPD) is characterized by low pulmonary function, inflammation, free radical production, vascular dysfunction, and subsequently a greater incidence of cardiovascular disease. By administering an acute oral antioxidant cocktail to patients with COPD (n=30) and controls (n=30), we sought to determine the role of redox balance in the vascular dysfunction of these patients. Using a double-blind, randomized, placebo-controlled, crossover design, patients with COPD and controls were ingested placebo or the antioxidant cocktail (vitamin C, vitamin E, α-lipoic acid) after which brachial artery flow-mediated dilation and carotid-radial pulse wave velocity were assessed using ultrasound Doppler. The patients exhibited lower baseline antioxidant levels (vitamin C and superoxide dismutase activity) and higher levels of oxidative stress (thiobarbituic acid reactive species) in comparison with controls. The patients also displayed lower basal flow-mediated dilation (P0.05; placebo versus antioxidant cocktail). The antioxidant cocktail also improved pulse wave velocity in patients with COPD (14±1 versus 11±1 m·s−1; P0.05; placebo versus antioxidant). Patients with COPD exhibit vascular dysfunction, likely mediated by an altered redox balance, which can be acutely mitigated by an oral antioxidant. Therefore, free radically mediated vascular dysfunction may be an important mechanism contributing to this population’s greater risk and incidence of cardiovascular disease.
    LanguageEnglish
    JournalHypertension
    Volume63
    DOIs
    Publication statusPublished - 9 Dec 2013

    Fingerprint

    Chronic Obstructive Pulmonary Disease
    Oxidation-Reduction
    Blood Vessels
    Antioxidants
    Placebos
    Pulse Wave Analysis
    Ascorbic Acid
    Dilatation
    Cardiovascular Diseases
    Thioctic Acid
    Doppler Ultrasonography
    Brachial Artery
    Incidence
    Vitamin E
    Cross-Over Studies
    Superoxide Dismutase
    Free Radicals
    Pneumonia
    Oxidative Stress
    Acids

    Keywords

    • free radicals
    • oxidative stress
    • pulmonary disease
    • chronic obstructive
    • vascular stiffness

    Cite this

    Ives, S. J., Harris, R. A., Witman, M. A. H., Fjeldstad, M. A. H., Garten, R. S., McDaniel, J., ... Richardson, R. S. (2013). Vascular Dysfunction and Chronic Obstructive Pulmonary Disease: The Role of Redox Balance. Hypertension, 63. https://doi.org/10.1161/HYPERTENSIONAHA.113.02255
    Ives, Stephen J ; Harris, Ryan A. ; Witman, Melissa A H ; Fjeldstad, Melissa A H ; Garten, Ryan S ; McDaniel, John ; Wray, D Walter ; Richardson, Russell S. / Vascular Dysfunction and Chronic Obstructive Pulmonary Disease: The Role of Redox Balance. In: Hypertension. 2013 ; Vol. 63.
    @article{bfbf41cabf174b53bcc7bdb8f54badbc,
    title = "Vascular Dysfunction and Chronic Obstructive Pulmonary Disease: The Role of Redox Balance",
    abstract = "Chronic obstructive pulmonary disease (COPD) is characterized by low pulmonary function, inflammation, free radical production, vascular dysfunction, and subsequently a greater incidence of cardiovascular disease. By administering an acute oral antioxidant cocktail to patients with COPD (n=30) and controls (n=30), we sought to determine the role of redox balance in the vascular dysfunction of these patients. Using a double-blind, randomized, placebo-controlled, crossover design, patients with COPD and controls were ingested placebo or the antioxidant cocktail (vitamin C, vitamin E, α-lipoic acid) after which brachial artery flow-mediated dilation and carotid-radial pulse wave velocity were assessed using ultrasound Doppler. The patients exhibited lower baseline antioxidant levels (vitamin C and superoxide dismutase activity) and higher levels of oxidative stress (thiobarbituic acid reactive species) in comparison with controls. The patients also displayed lower basal flow-mediated dilation (P0.05; placebo versus antioxidant cocktail). The antioxidant cocktail also improved pulse wave velocity in patients with COPD (14±1 versus 11±1 m·s−1; P0.05; placebo versus antioxidant). Patients with COPD exhibit vascular dysfunction, likely mediated by an altered redox balance, which can be acutely mitigated by an oral antioxidant. Therefore, free radically mediated vascular dysfunction may be an important mechanism contributing to this population’s greater risk and incidence of cardiovascular disease.",
    keywords = "free radicals, oxidative stress, pulmonary disease, chronic obstructive, vascular stiffness",
    author = "Ives, {Stephen J} and Harris, {Ryan A.} and Witman, {Melissa A H} and Fjeldstad, {Melissa A H} and Garten, {Ryan S} and John McDaniel and Wray, {D Walter} and Richardson, {Russell S}",
    note = "Reference text: 1. Divo M, Cote C, de Torres JP, Casanova C, Marin JM, Pinto-Plata V, Zulueta J, Cabrera C, Zagaceta J, Hunninghake G, Celli B; BODE Collaborative Group. Comorbidities and risk of mortality in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;186:155–161. 2. Macnee W, Maclay J, McAllister D. Cardiovascular injury and repair in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008;5:824–833. 3. Konecny T, Somers K, Orban M, Koshino Y, Lennon RJ, Scanlon PD, Rihal CS. Interactions between COPD and outcomes after percutaneous coronary intervention. Chest. 2010;138:621–627. 4. Barnes PJ, Celli BR. Systemic manifestations and comorbidities of COPD. Eur Respir J. 2009;33:1165–1185. 5. Luppi F, Franco F, Begh{\'e} B, Fabbri LM. Treatment of chronic obstructive pulmonary disease and its comorbidities. Proc Am Thorac Soc. 2008;5:848–856. 6. Sin DD, Wu L, Man SF. The relationship between reduced lung function and cardiovascular mortality: a population-based study and a systematic review of the literature. Chest. 2005;127:1952–1959. 7. Matsuoka S, Yamashiro T, Diaz A, Est{\'e}par RS, Ross JC, Silverman EK, Kobayashi Y, Dransfield MT, Bartholmai BJ, Hatabu H, Washko GR. The relationship between small pulmonary vascular alteration and aortic atherosclerosis in chronic obstructive pulmonary disease: quantitative CT analysis. Acad Radiol. 2011;18:40–46. 8. Stone IS, Barnes NC, Petersen SE. Chronic obstructive pulmonary disease: a modifiable risk factor for cardiovascular disease? Heart. 2012;98:1055–1062. 9. Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992;340:1111–1115. 10. Yeboah J, Crouse JR, Hsu FC, Burke GL, Herrington DM. Brachial flowmediated dilation predicts incident cardiovascular events in older adults: the Cardiovascular Health Study. Circulation. 2007;115:2390–2397. 11. Yeboah J, Folsom AR, Burke GL, Johnson C, Polak JF, Post W, Lima JA, Crouse JR, Herrington DM. Predictive value of brachial flow-mediated dilation for incident cardiovascular events in a population-based study: the multi-ethnic study of atherosclerosis. Circulation. 2009;120:502–509. 12. Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D, Lieberman EH, Ganz P, Creager MA, Yeung AC. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol. 1995;26:1235–1241. 13. Yeboah J, Sutton-Tyrrell K, Mcburnie M, Burke G, Herrington D, Crouse J. Association between brachial artery reactivity and cardiovascular disease status in an elderly cohort: the cardiovascular health study. Atherosclerosis. 2008;197:768–776. 14. Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol. 2010;55:1318–1327. 15. Chirinos JA, Kips JG, Jacobs DR Jr, Brumback L, Duprez DA, Kronmal R, Bluemke DA, Townsend RR, Vermeersch S, Segers P. Arterial wave reflections and incident cardiovascular events and heart failure: MESA (Multiethnic Study of Atherosclerosis). J Am Coll Cardiol. 2012;60:2170–2177. 16. Weber T, Auer J, O’Rourke MF, Kvas E, Lassnig E, Berent R, Eber B. Arterial stiffness, wave reflections, and the risk of coronary artery disease. Circulation. 2004;109:184–189. 17. Ozben B, Ery{\"u}ksel E, Tanrikulu AM, Papila-Topal N, Celikel T, Başaran Y. Acute exacerbation impairs endothelial function in patients with chronic obstructive pulmonary disease. Turk Kardiyol Dern Ars. 2010;38:1–7. 18. Eickhoff P, Valipour A, Kiss D, Schreder M, Cekici L, Geyer K, Kohansal R, Burghuber OC. 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    year = "2013",
    month = "12",
    day = "9",
    doi = "10.1161/HYPERTENSIONAHA.113.02255",
    language = "English",
    volume = "63",
    journal = "Hypertension",
    issn = "0194-911X",

    }

    Ives, SJ, Harris, RA, Witman, MAH, Fjeldstad, MAH, Garten, RS, McDaniel, J, Wray, DW & Richardson, RS 2013, 'Vascular Dysfunction and Chronic Obstructive Pulmonary Disease: The Role of Redox Balance', Hypertension, vol. 63. https://doi.org/10.1161/HYPERTENSIONAHA.113.02255

    Vascular Dysfunction and Chronic Obstructive Pulmonary Disease: The Role of Redox Balance. / Ives, Stephen J; Harris, Ryan A.; Witman, Melissa A H; Fjeldstad, Melissa A H; Garten, Ryan S; McDaniel, John; Wray, D Walter; Richardson, Russell S.

    In: Hypertension, Vol. 63, 09.12.2013.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Vascular Dysfunction and Chronic Obstructive Pulmonary Disease: The Role of Redox Balance

    AU - Ives, Stephen J

    AU - Harris, Ryan A.

    AU - Witman, Melissa A H

    AU - Fjeldstad, Melissa A H

    AU - Garten, Ryan S

    AU - McDaniel, John

    AU - Wray, D Walter

    AU - Richardson, Russell S

    N1 - Reference text: 1. Divo M, Cote C, de Torres JP, Casanova C, Marin JM, Pinto-Plata V, Zulueta J, Cabrera C, Zagaceta J, Hunninghake G, Celli B; BODE Collaborative Group. Comorbidities and risk of mortality in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2012;186:155–161. 2. Macnee W, Maclay J, McAllister D. Cardiovascular injury and repair in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008;5:824–833. 3. Konecny T, Somers K, Orban M, Koshino Y, Lennon RJ, Scanlon PD, Rihal CS. Interactions between COPD and outcomes after percutaneous coronary intervention. Chest. 2010;138:621–627. 4. Barnes PJ, Celli BR. Systemic manifestations and comorbidities of COPD. Eur Respir J. 2009;33:1165–1185. 5. Luppi F, Franco F, Beghé B, Fabbri LM. Treatment of chronic obstructive pulmonary disease and its comorbidities. Proc Am Thorac Soc. 2008;5:848–856. 6. Sin DD, Wu L, Man SF. The relationship between reduced lung function and cardiovascular mortality: a population-based study and a systematic review of the literature. Chest. 2005;127:1952–1959. 7. Matsuoka S, Yamashiro T, Diaz A, Estépar RS, Ross JC, Silverman EK, Kobayashi Y, Dransfield MT, Bartholmai BJ, Hatabu H, Washko GR. The relationship between small pulmonary vascular alteration and aortic atherosclerosis in chronic obstructive pulmonary disease: quantitative CT analysis. Acad Radiol. 2011;18:40–46. 8. Stone IS, Barnes NC, Petersen SE. Chronic obstructive pulmonary disease: a modifiable risk factor for cardiovascular disease? Heart. 2012;98:1055–1062. 9. Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992;340:1111–1115. 10. Yeboah J, Crouse JR, Hsu FC, Burke GL, Herrington DM. Brachial flowmediated dilation predicts incident cardiovascular events in older adults: the Cardiovascular Health Study. Circulation. 2007;115:2390–2397. 11. Yeboah J, Folsom AR, Burke GL, Johnson C, Polak JF, Post W, Lima JA, Crouse JR, Herrington DM. Predictive value of brachial flow-mediated dilation for incident cardiovascular events in a population-based study: the multi-ethnic study of atherosclerosis. Circulation. 2009;120:502–509. 12. Anderson TJ, Uehata A, Gerhard MD, Meredith IT, Knab S, Delagrange D, Lieberman EH, Ganz P, Creager MA, Yeung AC. Close relation of endothelial function in the human coronary and peripheral circulations. J Am Coll Cardiol. 1995;26:1235–1241. 13. Yeboah J, Sutton-Tyrrell K, Mcburnie M, Burke G, Herrington D, Crouse J. Association between brachial artery reactivity and cardiovascular disease status in an elderly cohort: the cardiovascular health study. Atherosclerosis. 2008;197:768–776. 14. Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol. 2010;55:1318–1327. 15. Chirinos JA, Kips JG, Jacobs DR Jr, Brumback L, Duprez DA, Kronmal R, Bluemke DA, Townsend RR, Vermeersch S, Segers P. Arterial wave reflections and incident cardiovascular events and heart failure: MESA (Multiethnic Study of Atherosclerosis). J Am Coll Cardiol. 2012;60:2170–2177. 16. Weber T, Auer J, O’Rourke MF, Kvas E, Lassnig E, Berent R, Eber B. Arterial stiffness, wave reflections, and the risk of coronary artery disease. Circulation. 2004;109:184–189. 17. Ozben B, Eryüksel E, Tanrikulu AM, Papila-Topal N, Celikel T, Başaran Y. Acute exacerbation impairs endothelial function in patients with chronic obstructive pulmonary disease. Turk Kardiyol Dern Ars. 2010;38:1–7. 18. Eickhoff P, Valipour A, Kiss D, Schreder M, Cekici L, Geyer K, Kohansal R, Burghuber OC. Determinants of systemic vascular function in patients with stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008;178:1211–1218. 19. Barr RG, Mesia-Vela S, Austin JHM, Basner RC, Keller BM, Reeves AP, Shimbo D, Stevenson L. Impaired flow-mediated dilation is associated with low pulmonary function and emphysema in ex-smokers. Am J Respir Crit Care Med 2007;176:1200–1207. 20. Maclay JD, McAllister DA, Mills NL, Paterson FP, Ludlam CA, Drost EM, Newby DE, Macnee W. Vascular dysfunction in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2009;180:513–520. 21. Maclay JD, McAllister DA, Rabinovich R, Haq I, Maxwell S, Hartland S, Connell M, Murchison JT, van Beek EJ, Gray RD, Mills NL, Macnee W. Systemic elastin degradation in chronic obstructive pulmonary disease. Thorax. 2012;67:606–612. 22. Vivodtzev I, Minet C, Wuyam B, Borel JC, Vottero G, Monneret D, Baguet JP, Lévy P, Pépin JL. Significant improvement in arterial stiffness after endurance training in patients with COPD. Chest. 2010;137:585–592. 23. Alford SK, van Beek EJ, McLennan G, Hoffman EA. Heterogeneity of pulmonary perfusion as a mechanistic image-based phenotype in emphysema susceptible smokers. Proc Natl Acad Sci U S A. 2010;107:7485–7490. 24. Arao T, Takabatake N, Sata M, Abe S, Shibata Y, Honma T, Takahashi K, Okada A, Takeishi Y, Kubota I. In vivo evidence of endothelial injury in chronic obstructive pulmonary disease by lung scintigraphic assessment of (123)I-metaiodobenzylguanidine. J Nucl Med. 2003;44:1747–1754. 25. Peinado VI, Barbera JA, Ramirez J, Gomez FP, Roca J, Jover L, Gimferrer JM, Rodriguez-Roisin R. Endothelial dysfunction in pulmonary arteries of patients with mild COPD. Am J Physiol. 1998;274(6 Pt 1):L908–L913. 26. Chao J, Wood JG, Gonzalez NC. Alveolar macrophages initiate the systemic microvascular inflammatory response to alveolar hypoxia. Respir Physiol Neurobiol. 2011;178:439–448. 27. Sabit R, Shale DJ. Vascular structure and function in chronic obstructive pulmonary disease: a chicken and egg issue? Am J Respir Crit Care Med. 2007;176:1175–1176. 28. Folchini F, Nonato NL, Feofiloff E, D’Almeida V, Nascimento O, Jardim JR. Association of oxidative stress markers and C-reactive protein with multidimensional indexes in COPD. Chron Respir Dis. 2011;8:101–108. 29. Eagan TM, Ueland T, Wagner PD, Hardie JA, Mollnes TE, Damås JK, Aukrust P, Bakke PS. Systemic inflammatory markers in COPD: results from the Bergen COPD Cohort Study. Eur Respir J. 2010;35:540–548. 30. Pinto-Plata VM, Müllerova H, Toso JF, Feudjo-Tepie M, Soriano JB, Vessey RS, Celli BR. C-reactive protein in patients with COPD, control smokers and non-smokers. Thorax. 2006;61:23–28. 31. Celli BR, Locantore N, Yates J, et al; ECLIPSE Investigators. Inflammatory biomarkers improve clinical prediction of mortality in chronic obstructive pulmonary disease. 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    PY - 2013/12/9

    Y1 - 2013/12/9

    N2 - Chronic obstructive pulmonary disease (COPD) is characterized by low pulmonary function, inflammation, free radical production, vascular dysfunction, and subsequently a greater incidence of cardiovascular disease. By administering an acute oral antioxidant cocktail to patients with COPD (n=30) and controls (n=30), we sought to determine the role of redox balance in the vascular dysfunction of these patients. Using a double-blind, randomized, placebo-controlled, crossover design, patients with COPD and controls were ingested placebo or the antioxidant cocktail (vitamin C, vitamin E, α-lipoic acid) after which brachial artery flow-mediated dilation and carotid-radial pulse wave velocity were assessed using ultrasound Doppler. The patients exhibited lower baseline antioxidant levels (vitamin C and superoxide dismutase activity) and higher levels of oxidative stress (thiobarbituic acid reactive species) in comparison with controls. The patients also displayed lower basal flow-mediated dilation (P0.05; placebo versus antioxidant cocktail). The antioxidant cocktail also improved pulse wave velocity in patients with COPD (14±1 versus 11±1 m·s−1; P0.05; placebo versus antioxidant). Patients with COPD exhibit vascular dysfunction, likely mediated by an altered redox balance, which can be acutely mitigated by an oral antioxidant. Therefore, free radically mediated vascular dysfunction may be an important mechanism contributing to this population’s greater risk and incidence of cardiovascular disease.

    AB - Chronic obstructive pulmonary disease (COPD) is characterized by low pulmonary function, inflammation, free radical production, vascular dysfunction, and subsequently a greater incidence of cardiovascular disease. By administering an acute oral antioxidant cocktail to patients with COPD (n=30) and controls (n=30), we sought to determine the role of redox balance in the vascular dysfunction of these patients. Using a double-blind, randomized, placebo-controlled, crossover design, patients with COPD and controls were ingested placebo or the antioxidant cocktail (vitamin C, vitamin E, α-lipoic acid) after which brachial artery flow-mediated dilation and carotid-radial pulse wave velocity were assessed using ultrasound Doppler. The patients exhibited lower baseline antioxidant levels (vitamin C and superoxide dismutase activity) and higher levels of oxidative stress (thiobarbituic acid reactive species) in comparison with controls. The patients also displayed lower basal flow-mediated dilation (P0.05; placebo versus antioxidant cocktail). The antioxidant cocktail also improved pulse wave velocity in patients with COPD (14±1 versus 11±1 m·s−1; P0.05; placebo versus antioxidant). Patients with COPD exhibit vascular dysfunction, likely mediated by an altered redox balance, which can be acutely mitigated by an oral antioxidant. Therefore, free radically mediated vascular dysfunction may be an important mechanism contributing to this population’s greater risk and incidence of cardiovascular disease.

    KW - free radicals

    KW - oxidative stress

    KW - pulmonary disease

    KW - chronic obstructive

    KW - vascular stiffness

    U2 - 10.1161/HYPERTENSIONAHA.113.02255

    DO - 10.1161/HYPERTENSIONAHA.113.02255

    M3 - Article

    VL - 63

    JO - Hypertension

    T2 - Hypertension

    JF - Hypertension

    SN - 0194-911X

    ER -