Basic Science Research| Volume 52, P216-224, October 2018

Download started.


Oxidative Stress in Aortas of Patients with Advanced Occlusive and Aneurysmal Diseases


      Aortoiliac occlusive disease (AOD) and abdominal aortic aneurysm (AAA) are very important cardiovascular diseases that present different aspects of pathophysiology; however, oxidative stress and inflammatory response seem be relevant in both of them. Our objective was to evaluate oxidative damage and degree of inflammatory infiltrate in aortas of patients surgically treated for AOD and AAA.

      Materials and Methods

      Levels of reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and myeloperoxidase (MPO) expression as well as nitrite levels and superoxide dismutase (SOD) and catalase (CAT) activities were evaluated in aortas of patients with AOD (n = 16) or AAA (n = 14), while the control group was formed by cadaveric organ donors (n = 10). We also analyzed the degree of inflammatory infiltrate in these aortas.


      There was an increase in ROS levels and NADPH oxidase activity in patients with AOD and AAA when compared with the control group, and the AOD group demonstrated higher ROS production and NADPH oxidase activity and also nitrite levels when compared with the AAA group (P < 0.001). On the other hand, an increase of SOD activity in the AOD group and CAT activity in the AAA group was observed. Inflammatory infiltrate and MPO expression were higher in the AOD group when compared with the control group (P < 0.05).


      Oxidative stress is relevant in both AOD and AAA, though AOD presented higher ROS levels and NADPH activity. Increased activities of antioxidant enzymes may be a compensatory phenomenon which occurs in aortas of patients with AOD and AAA. Perhaps, a relationship between oxidative stress and degree of inflammatory infiltrate may exist in the pathophysiology of AOD and AAA.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Annals of Vascular Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Nordom I.M.
        • Hinchliffe R.J.
        • Loftus I.M.
        • et al.
        Pathophysiology and epidemiology of abdominal aortic aneurysms.
        Nat Rev Cardiol. 2011; 8: 92-102
        • Indes J.E.
        • Pfaff M.J.
        • Farrokhyar F.
        • et al.
        Clinical outcomes of 5358 patients undergoing direct open bypass or endovascular treatment for aortoiliac occlusive disease: a systematic review and meta-analysis.
        J Endovasc Ther. 2013; 20: 443-455
        • Norgren L.
        • Hiatt W.R.
        • Dormandy J.A.
        • et al.
        Inter-society consensus for the management of peripheral arterial disease.
        Int Angiol. 2007; 26: 81-157
        • Gimbrone Jr., M.A.
        • García-Cardeña G.
        Endothelial cell dysfunction and the pathobiology of atherosclerosis.
        Circ Res. 2016; 118: 620-636
        • Weintraub N.L.
        Understanding abdominal aortic aneurysm.
        N Engl J Med. 2009; 361: 1114-1116
        • Förstermann U.
        Oxidative stress in vascular disease: causes, defense mechanisms and potential therapies.
        Nat Clin Pract Cardiovasc Med. 2008; 326: 745-753
        • Singh U.
        • Jialal I.
        Oxidative stress and atherosclerosis.
        Pathophysiology. 2006; 13: 129-142
        • Miller Jr., F.J.
        • Sharp W.J.
        • Fang X.
        • et al.
        Oxidative stress in human abdominal aortic aneurysms: a potential mediator of aneurysmal remodeling.
        Arterioscler Thromb Vasc Biol. 2002; 22: 560-565
        • Brown D.I.
        • Griendling K.K.
        Regulation of signal transduction by reactive oxygen species in the cardiovascular system.
        Circ Res. 2015; 116: 531-549
        • Förstermann U.
        Nitric oxide and oxidative stress in vascular disease.
        Pflugers Arch. 2010; 459: 923-939
        • Zhang J.
        • Schmidt J.
        • Ryschich E.
        • et al.
        Inducible nitric oxide synthase is present in human abdominal aortic aneurysm and promotes oxidative vascular injury.
        J Vasc Surg. 2003; 38: 360-367
        • Förstermann U.
        • Xia N.
        • Li H.
        Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis.
        Circ Res. 2017; 120: 713-735
        • Emeto T.I.
        • Moxon J.V.
        • Au M.
        • et al.
        Oxidative stress and abdominal aortic aneurysm: potential treatment targets.
        Clin Sci (Lond). 2016; 130: 301-315
        • Dubick M.A.
        • Keen C.L.
        • DiSilvestro R.A.
        • et al.
        Antioxidant enzyme activity in human abdominal aortic aneurysmal and occlusive disease.
        Proc Soc Exp Biol Med. 1999; 220: 39-45
        • Sartorio C.L.
        • Fraccarollo D.
        • Galuppo P.
        • et al.
        Mineralocorticoid receptor blockade improve vasomotor dysfunction and vascular oxidative stress after myocardial infarction.
        Hypertension. 2007; 50: 919-925
        • LeBel C.P.
        • Ischiropoulos H.
        • Bondy S.C.
        Evaluation of the probe 2',7'-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress.
        Chem Res Toxicol. 1992; 5: 227-231
        • Wei Y.
        • Sowers J.R.
        • Nistala R.
        • et al.
        Angiotensin II-induced NADPH oxidase activation impairs insulin signaling in skeletal muscle cells.
        J Biol Chem. 2006; 281: 35137-35146
        • Marklund S.L.
        Superoxide dismutase isoenzymes in tissues and plasma from New Zealand black mice, nude mice and normal BALB/c mice.
        Mutat Res. 1985; 148: 129-134
        • Aebi H.
        Catalase in vitro.
        Methods Enzymol. 1984; 105: 121-126
        • Granger D.L.
        • Anstey N.M.
        • Miller W.C.
        • et al.
        Measuring nitric oxide production in human clinical studies.
        Methods Enzymol. 1999; 301: 49-61
        • Lowry O.H.
        • Rosebrough N.J.
        • Farr A.L.
        • et al.
        Protein measurement with the folin phenol reagent.
        J Biol Chem. 1951; 193: 265-275
        • Monteiro J.A.T.
        • da Silva E.S.
        • Raghavan M.L.
        • et al.
        Histologic, histochemical, and biochemical properties of fragments isolated from anterior wall of abdominal aortic aneurysms.
        J Vasc Surg. 2014; 59: 1393-1401
        • Brown K.E.
        • Brunt E.M.
        • Heinecke J.W.
        Immunohistochemical detection of myeloperoxidase and its oxidation products in Kupffer cells of human liver.
        Am J Pathol. 2001; 159: 2081-2088
        • Dilek N.
        • Dilek A.R.
        • Taskin Y.
        • et al.
        Contribution of myeloperoxidase and inducible nitric oxide synthase to pathogenesis of psoriasis.
        Adv Dermatol Allergol. 2016; 33: 435-439
        • McCormick M.L.
        • Gavrilla D.
        • Weintraub N.L.
        Role of oxidative stress in the pathogenesis of abdominal aortic aneurysms.
        Arterioscler Thromb Vasc Biol. 2007; 27: 461-469
        • Pastori D.
        • Carnevale R.
        • Pugnatelli P.
        Is there a clinical role for oxidative stress biomarkers in atherosclerotic diseases?.
        Intern Emerg Med. 2014; 9: 123-131
        • Manea A.
        NADPH oxidase-derived reactive oxygen species: involvement in vascular physiology and pathology.
        Cell Tissue Res. 2010; 342: 325-339
        • Kinkade K.
        • Streeter J.
        • Miller F.J.
        Inhibition of NADPH oxidase by apocynin attenuates progression of atherosclerosis.
        Int J Mol Sci. 2013; 14: 17017-17028
        • Beloqui O.
        • Moreno M.U.
        • San José G.
        • et al.
        Increased phagocytic NADPH oxidase activity associates with coronary artery calcification in asymptomatic men.
        Free Radic Res. 2017; 51: 389-396
        • Ejiri J.
        • Inoue N.
        • Tsukube T.
        • et al.
        Oxidative stress in the pathogenesis of thoracic aortic aneurysm: protective role of statin and angiotensin II type 1 receptor blocker.
        Cardiovasc Res. 2003; 59: 988-996
        • Guzik B.
        • Sagan A.
        • Ludew D.
        • et al.
        Mechanisms of oxidative stress in human aortic aneurysms: association with clinical risk factors for atherosclerosis and disease severity.
        Int J Cardiol. 2013; 168: 2389-2396
        • Liu C.
        • Desikan R.
        • Ying Z.
        • et al.
        Effects of a novel pharmacologic inhibitor of myeloperoxidase in a mouse atherosclerosis model.
        PLoS One. 2012; 7: e50767
        • Brevetti G.
        • Schiano V.
        • Laurenzano E.
        • et al.
        Myeloperoxidase, but not C-reactive protein, predicts cardiovascular risk in peripheral arterial disease.
        Eur Heart J. 2008; 29: 224-230
        • Meuwese M.C.
        • Stroes E.S.
        • Hazen S.L.
        • et al.
        Serum myeloperoxidase levels are associated with the future risk of coronary artery disease in apparently healthy individuals: the EPIC-Norfolk Prospective Population Study.
        J Am Coll Cardiol. 2007; 50: 159-165
        • Daugherty A.
        • Dunn J.L.
        • Rateri D.L.
        • et al.
        Myeloperoxidase, a catalyst for lipoprotein oxidation, is expressed in human atherosclerotic lesions.
        J Clin Invest. 1994; 94: 437-444
        • Hazell L.J.
        • Arnold L.
        • Flowers D.
        • et al.
        Presence of hypochlorite-modified proteins in human atherosclerotic lesions.
        J Clin Invest. 1996; 97: 1535-1544
        • Fukai T.
        • Ushio-Fukai M.
        Superoxide dismutases: role in redox signaling, vascular function, and diseases.
        Antioxid Redox Signal. 2011; 15: 1583-1606
        • Yu Z.
        • Morimoto K.
        • Yu J.
        • et al.
        Endogenous superoxide dismutase activation by oral administration of riboflavin reduces abdominal aortic aneurysm formation in rats.
        J Vasc Surg. 2016; 64: 737-745
        • Yajima N.
        • Masuda M.
        • Miyazaki M.
        • et al.
        Oxidative stress is involved in the development of experimental abdominal aortic aneurysm: a study of the transcription profile with complementary DNA microarray.
        J Vasc Surg. 2002; 36: 379-385
        • Lin S.J.
        • Shyue S.K.
        • Shih M.C.
        • et al.
        Superoxide dismutase and catalase inhibit oxidized low-density lipoprotein-induced human aortic smooth muscle cell proliferation: role of cell-cycle regulation, mitogen-activated protein kinases, and transcription factors.
        Atherosclerosis. 2007; 190: 124-134
        • Parastatidis I.
        • Weiss D.
        • Joseph G.
        • et al.
        Overexpression of catalase in vascular smooth muscle cells prevents the formation of abdominal aortic aneurysms.
        Arterioscler Thromb Vasc Biol. 2013; 33: 2389-2396
        • Li H.
        • Horke S.
        • Forstermann U.
        Vascular oxidative stress, nitric oxide and atherosclerosis.
        Atherosclerosis. 2014; 237: 208-219
        • Soto M.E.
        • Soria-Castro E.
        • Lans V.G.
        • et al.
        Analysis of oxidative stress enzymes and structural and functional proteins on human aortic tissue from different aortopathies.
        Oxid Med Cell Longev. 2014; 2014: 760694
        • Liao M.F.
        • Jing Z.P.
        • Bao J.M.
        • et al.
        Role of nitric oxide and inducible nitric oxide synthase in human abdominal aortic aneurysms: a preliminary study.
        Chin Med J. 2006; 119: 312-318
        • Johanning J.M.
        • Franklin D.P.
        • Han D.C.
        • et al.
        Inhibition of inducible nitric oxide synthase limits nitric oxide production and experimental aneurysm expansion.
        J Vasc Surg. 2001; 33: 579-586
        • Davies M.J.
        Myeloperoxidase-derived oxidation: mechanisms of biological damage and its prevention.
        J Clin Biochem Nutr. 2011; 48: 8-19
        • Madigan M.
        • Zuckerbraun B.
        Therapeutic potential of the nitrite-generated no pathway in vascular dysfunction.
        Front Immunol. 2013; 4
        • Paik D.
        • Tilson M.D.
        Neovascularization in the abdominal aortic aneurysm. Endothelial nitric oxide synthase, nitric oxide, and elastolysis.
        Ann N Y Acad Sci. 1996; 800: 277
        • Cochain C.
        • Zernecke A.
        Macrophages in vascular inflammation and atherosclerosis.
        Pflugers Arch. 2017; 469: 485-499
        • Guo D.C.
        • Papke C.L.
        • He R.
        • et al.
        Pathogenesis of thoracic and abdominal aortic aneurysms.
        Ann N Y Acad Sci. 2006; 1085: 339-352
        • Golledge A.L.
        • Walker P.
        • Norman P.E.
        • et al.
        A systematic review of studies examining inflammation associated cytokines in human abdominal aortic aneurysm samples.
        Dis Markers. 2009; 26: 181-188
        • Mikolajczyk-Stecyna J.
        • Korcz A.
        • Gabriel M.
        • et al.
        Risk factors in abdominal aortic aneurysm and in Polish population aortoiliac occlusive disease and differences between them.
        Sci Rep. 2013; 3: 3528
        • Pimiento J.M.
        • Maloney S.P.
        • Tang P.C.Y.
        • et al.
        Endothelial nitric oxide synthase stimulates aneurysm growth in aged mice.
        J Vasc Res. 2008; 45: 251-258