Background: Pro-oxidative stress and pro-inflammatory responses can influence each other in the development of atherosclerosis. This study evaluated the relationship between oxidative stress, inflammation, and multiple peripheral artery occlusions in elderly patients (age mean 71.2 ± 8.1 years). Methods: A total of 723 participants were enrolled: 67 healthy subjects, 214 patients with common iliac artery occlusions, 224 patients with popliteal artery occlusions, and 218 patients with femoral artery occlusions. We measured oxidative stress biomarkers (malondialdehyde [MDA], F2-isoprostane [F2-isoP], total oxidant status [TOS], and ischemia-modified albumin [IMA]) and the expressions of molecules in mimecan (MIME)/nuclear factor kappa B (NF-κB)/P53/Toll-like receptor 4 (TLR4) signaling pathway in older patients with multiple peripheral artery occlusions. Results: The levels of MDA, F2-isoP, TOS, IMA, MIME, NF-κB, P53, and TLR4 were increased in the single-site peripheral artery occlusive group when compared with healthy controls (P < .001) and were further increased in the multiple-site peripheral artery occlusive group compared with the single-site peripheral artery occlusive group (P < .001). Conclusion: Oxidative stress may promote inflammatory signaling pathways and lead to multiple peripheral artery occlusions in elderly patients.
KhosraviMPoursalehAGhasempourGFarhadSNajafiM. The effects of oxidative stress on the development of atherosclerosis. Biol Chem. 2019;400:711-732.
2.
Reyes-GordilloKShahRMurielP. Oxidative stress and inflammation in hepatic diseases: current and future therapy. Oxid Med Cell Longev. 2017;2017:3140673.
3.
OumiTNozatoTSakakibaraA, et al.Malondialdehyde-modified low density lipoprotein as oxidative-stress marker in vasospastic angina patients. Int Heart J. 2017;58:335-343.
4.
LorenzanoSRostNSKhanM, et al.Oxidative stress biomarkers of brain damage: hyperacute plasma F2-isoprostane predicts infarct growth in stroke. Stroke. 2018;49:630-637.
5.
VermaAKRajJSharmaVSinghTBSrivastavaSSrivastavaR. Plasma prolidase activity and oxidative stress in patients with Parkinson’s disease. Parkinsons Dis. 2015;2015:598028.
6.
AtaşHGönülMÖztürkYKavutçuM. Ischemic modified albumin as a new biomarker in predicting oxidative stress in alopecia areata. Turk J Med Sci. 2019;9:129-138.
7.
TengrydCNielsenSHCavaleraM, et al.The proteoglycan mimecan is associated with carotid plaque vulnerability and increased risk of future cardiovascular death. Atherosclerosis. 2020;313:88-95.
8.
ZhangHWangJLiuHZhangXZhanMChenF. Overexpression of mimecan in human aortic smooth muscle cells inhibits cell proliferation and enhances apoptosis and migration. Exp Ther Med. 2015;10:187-192.
9.
HuYLiuJZhaoQ, et al.Correlation between mimecan expression and coronary artery stenosis in patients with coronary heart disease. Int J Clin Exp Med. 2015;8:21641-21646.
10.
WangWBerghADamberJE. Increased p53 immunoreactivity in proliferative inflammatory atrophy of prostate is related to focal acute inflammation. APMIS. 2009;117:185-195.
11.
LoweJMMenendezDBushelPR, et al.p53 and NF-κB coregulate proinflammatory gene responses in human macrophages. Cancer Res. 2014;74:2182-2192.
12.
RathoreMGirardCOhannaM, et al.Cancer cell-derived long pentraxin 3 (PTX3) promotes melanoma migration through a toll-like receptor 4 (TLR4)/NF-κB signaling pathway. Oncogene. 2019;38:5873-5889.
13.
VanackerPLambrouDEskandariA, et al.Improving prediction of recanalization in acute large-vessel occlusive stroke. J Thromb Haemostasis. 2014;12:814-821.
14.
CunierMNajafiASheikhGTBinkertCA. Alternative crossing technique for iliaco-femoro-popliteal CTOs with a catheter only. CVIR Endovasc. 2019;2:23.
15.
ZhaoWZhangJMengY, et al.Symptomatic atherosclerotic non-acute intracranial vertebral artery total occlusion: clinical features, imaging characteristics, endovascular recanalization, and follow-up outcomes. Front Neurol. 2020;11:598795.
16.
RašićIRašićAAkšamijaGRadovićS. The relationship between serum level of malondialdehyde and progression of colorectal cancer. Acta Clin Croat. 2018;57:411-416.
17.
ÇavuşoğluYKorkmazŞDemirtaşS, et al.Ischemia-modified albumin levels in patients with acute decompensated heart failure treated with dobutamine or levosimendan: IMA-HF study. Anatol J Cardiol. 2015;15:611-617.
18.
GuXZhaoLZhuJ, et al.Serum mimecan is associated with arterial stiffness in hypertensive patients. J Am Heart Assoc. 2015;4:e002010.
19.
YuMYeLBianJMaLZhengCGuoH. Effect of Jiawei Shenfu decoction on tumor necrosis factor-alpha and nuclear factor-kappa B in patients who have chronic heart failure with syndromes of deficiency of heart Yang. J Tradit Chin Med. 2019;39:418-424.
20.
SyedaTRizviHAHadiSMHashimASMKhanMH. Interrelationship of serum S100B and P53 in brain tumour patients. J Pakistan Med Assoc. 2016;66:748-750.
21.
LiTJingJYangJ, et al.Serum levels of matrix metalloproteinase 9 and toll-like receptor 4 in acute aortic dissection: a case-control study. BMC Cardiovasc Disord. 2018;18:219.
22.
DayamaATsilimparisNKolakowskiSMatoloNMHumphriesMD. Clinical outcomes of bypass-first versus endovascular-first strategy in patients with chronic limb-threatening ischemia due to infrageniculate arterial disease. J Vasc Surg. 2019;69:156-163.
23.
LinENguyenCHThomasSG. Completion and adherence rates to exercise interventions in intermittent claudication: traditional exercise versus alternative exercise - a systematic review. Eur J Prev Cardiol. 2019;26:1625-1633.
24.
DumitruARaduBMRaduMCretoiuSM. Muscle changes during atrophy. Adv Exp Med Biol. 2018;1088:73-92.
25.
LeeHYanoYChoSM, et al.Cardiovascular risk of isolated systolic or diastolic hypertension in young adults. Circulation. 2020;141:1778-1786.
26.
PetersmannAMüller-WielandDMüllerUA, et al.Definition, classification and diagnosis of diabetes mellitus. Exp Clin Endocrinol Diabetes. 2019;127:S1-S7.
27.
PereiraAMMorais-AlmeidaMSousaAS, et al.Environmental tobacco smoke exposure at home and smoking prevalence in the general Portuguese population-the INAsma study. Rev Port Pneumol. 2013;19:114-124.
28.
SungHSiegelRLTorreLA, et al.Global patterns in excess body weight and the associated cancer burden. CA Cancer J Clin. 2019;69:88-112.
29.
van der LeedenMSteultjensMDekkerJHPrinsAPDekkerJ. The relationship of disease duration to foot function, pain and disability in rheumatoid arthritis patients with foot complaints. Clin Exp Rheumatol. 2007;25:275-280.
30.
JeanblancJSautonPJeanblancV, et al.Face validity of a pre-clinical model of operant binge drinking: just a question of speed. Addiction Biol. 2019;24:664-675.
31.
LiRVazquezJNovakJ, et al.Patterns of care and treatment outcomes in patients age 80 or older with non-metastatic pancreatic cancer. J Geriatr Oncol. 2020;11:652-659.
32.
LugrinJRosenblatt-VelinNParapanovRLiaudetL. The role of oxidative stress during inflammatory processes. Biol Chem. 2014;395:203-230.
33.
VargheseJFPatelRYadavvUCS. Novel insights in the metabolic syndrome-induced oxidative stress and inflammation-mediated atherosclerosis. Curr Cardiol Rev. 2018;14:4-14.
34.
TakamuraTATsuchiyaTOdaM, et al.Circulating malondialdehyde-modified low-density lipoprotein (MDA-LDL) as a novel predictor of clinical outcome after endovascular therapy in patients with peripheral artery disease (PAD). Atherosclerosis. 2017;263:192-197.
35.
MorishitaTUzuiHNakanoA, et al.Number of endothelial progenitor cells in peripheral artery disease as a marker of severity and association with pentraxin-3, malondialdehyde-modified low-density lipoprotein and membrane type-1 matrix metalloproteinase. J Atherosclerosis Thromb. 2012;19:149-158.
36.
CristMBMelekhinVVBianA, et al.Higher serum iron is associated with increased oxidant stress in HIV-infected men. J Acquir Immune Defic Syndr. 2013;64:367-373.
37.
MilneGLMusiekESMorrowJD. F2-isoprostanes as markers of oxidative stress in vivo: an overview. Biomarkers. 2005;10:S10-S23.
38.
KucukAUsluAUIcliA, et al.The LDL/HDL ratio and atherosclerosis in ankylosing spondylitis. Z Rheumatol. 2017;76:58-63.
39.
ChengYSheenJHuWHungY. Polyphenols and oxidative stress in atherosclerosis-related ischemic heart disease and stroke. Oxid Med Cell Longev. 2017;2017:8526438.
40.
KucukAUsluAUArslanS, et al.Ischemia-modified albumin and atherosclerosis in patients with familial Mediterranean fever. Angiology. 2016;67:456-460.
41.
StakhnevaEMMeshcheryakovaIADemidovetEA, et al.A proteomic study of atherosclerotic plaques in men with coronary atherosclerosis. Diagnostics. 2019;9:177.
42.
YuXZhengXTangC, et al.Nuclear factor-κB activation as a pathological mechanism of lipid metabolism and atherosclerosis. Adv Clin Chem. 2015;70:1-30.
43.
WuGCaiJHanY, et al.LincRNA-p21 regulates neointima formation, vascular smooth muscle cell proliferation, apoptosis, and atherosclerosis by enhancing 53 activity. Circulation. 2014;130:1452-1465.
LiYWangYChenY, et al.Corilagin ameliorates atherosclerosis in peripheral artery disease via the toll-Like receptor-4 signaling pathway in vitro and in vivo. Front Immunol. 2020;11:1611.
46.
ReuterSGuptaSCChaturvediMMAggarwalBB. Oxidative stress, inflammation, and cancer: how are they linked?Free Radic Biol Med. 2010;4:1603-1616.
47.
MuryPChiricoENMuraMMillonACanet-SoulasEPialouxV. Oxidative stress and inflammation, key targets of atherosclerotic plaque progression and vulnerability: potential impact of physical activity. Sports Med. 2018;48:2725-2741.
48.
GaoTYuWLiuC. Mechanisms of ischemic stroke in patients with intracranial atherosclerosis: a high-resolution magnetic resonance imaging study. Exp Ther Med. 2014;7:1415-1419.
49.
ChhaiPRheeK. Effect of distal thickening and stiffening of plaque cap on arterial wall mechanics. Med Biol Eng Comput. 2018;56:2003-2013.
50.
NakajimaAMinamiYArakiM, et al.Optical coherence tomography predictors for a favorable vascular response to statin therapy. J Am Heart Assoc. 2021;10:e018205.
51.
Al-SmadiASAbdallaRNElmokademAH, et al.Diagnostic accuracy of high-resolution black-blood MRI in the evaluation of intracranial large-vessel arterial occlusions. AJNR Am J Neuroradiol. 2019;40:954-959.
52.
LuMCuiYPengPQiaoHCaiJZhaoX. Shape and location of carotid atherosclerotic plaque and intraplaque hemorrhage: a high-resolution magnetic resonance imaging study. J Atherosclerosis Thromb2019;26:720-727.
53.
CrombagGAJCSchreuderFHBMvan HoofRHM, et al.Microvasculature and intraplaque hemorrhage in atherosclerotic carotid lesions: a cardiovascular magnetic resonance imaging study. J Cardiovasc Magn Reson. 2019;21:15.
54.
TziakasDNChalikiasGPavlakiM, et al.Lysed erythrocyte membranes promote vascular calcification. Circulation. 2019;139:2032-2048.
55.
KamelHNaviBBMerklerAE, et al.Reclassification of ischemic stroke etiological subtypes on the basis of high-risk nonstenosing carotid plaque. Stroke2020;51:504-510.
56.
MorrisDRSkalinaTASinghTPMoxonJVGolledgeJ. Association of computed tomographic leg muscle characteristics with lower limb and cardiovascular events in patients with peripheral artery disease. J Am Heart Assoc. 2018;7:e009943.
57.
ScottDShore-LorentiCMcMillanLB, et al.Calf muscle density is independently associated with physical function in overweight and obese older adults. J Musculoskelet Neuronal Interact. 2018;18:9-17.
58.
HollebekeRBCushmanMSchlueterEFAllisonMA. Abdominal muscle density is inversely related to adiposity inflammatory mediators. Med Sci Sports Exerc. 2018;50:1495-1501.
59.
McDermottMMFerrucciLGonzalez-FreireM, et al.Skeletal muscle pathology in peripheral artery disease: a brief review. Arterioscler Thromb Vasc Biol. 2020;40:2577-2585.
60.
YeZAliZKleeGGMosleyTHKulloJI. Associations of candidate biomarkers of vascular disease with the ankle–brachial index and peripheral arterial disease. Am J Hypertens. 2013;26:495-502.
61.
TsaiHHuangJTsaiY, et al.Association between albumin and C-reactive protein and ankle-brachial index in haemodialysis. Nephrology. 2018;23:5-10.
62.
LeeMYHsiaoPJHuangJC, et al.Abnormally low or high ankle-brachial index is associated with the development of diabetic retinopathy in type 2 diabetes mellitus. Sci Rep. 2018;8:441.
63.
BąkEMarciszCKadłubowskaM, et al.Independent factors of changes of ankle-brachial index in peripheral arterial occlusive disease in elderly patients with or without diabetes. Int J Environ Res Publ Health. 2016;13:1103.
64.
EngoleYMLepiraFBNlanduYM, et al.Prognostic significance of abnormal ankle-brachial index among long-term hemodialysis patients in Kinshasa, the Democratic Republic of the Congo. Rambam Maimonides Med J. 2021;12:e0001.
65.
CluffKKellyAMKoutakisP, et al.Surface-enhanced Raman spectral biomarkers correlate with ankle brachial index and characterize leg muscle biochemical composition of patients with peripheral arterial disease. Phys Rep. 2014;2:12148.
66.
LovelockTDeanAMowCClaydonMCampbellW. Cystic adventitial disease presenting as occlusion of the external iliac artery: a rare manifestation. Vasc Endovasc Surg. 2021;55:389-391.
67.
KhawajaHFontC. Common and external iliac artery occlusion in Behçet’s disease: a case of anchoring bias. BMJ Case Rep. 2020;13:e236554.
68.
SousaLHDBaptista-SilvaJCVasconcelosVFlumignanRLNakanoLC. Internal iliac artery revascularisation versus internal iliac artery occlusion for endovascular treatment of aorto-iliac aneurysms. Cochrane Database Syst Rev. 2020;7:CD013168.
69.
GazzaniSEMassoniCBMarcato1CPaladiniIRossiC. Endovascular treatment of iliac artery rupture after septic embolization. Acta Biomed. 2019;90:339-342.
70.
KevenADurmazMS. The importance of community screening of asymptomatic elderly for peripheral arterial disease by Doppler ultrasound and ankle-brachial index. J Ultrason. 2017;17:235-240.
71.
BalkanayOOÖmeroğluSN. Approach to peripheral arterial disease in the elderly. Turk Kardiyol Dernegi Arsivi. 2017;45:96-101.
72.
YbarraLFRinfretS. Why and how should we treat chronic total occlusion? Evolution of state-of-the-art methods and future directions. Can J Cardiol. 2020;S0828-282X(20):31052-31057.
73.
TabasIBornfeldtKE. Intracellular and intercellular aspects of macrophage immunometabolism in atherosclerosis. Circ Res. 2020;126:1209-1227.
74.
SoaresRAMatieloMFNetoFB, et al.WIfI classification versus angiosome concept: a change in the infrapopliteal angioplasties paradigm. Ann Vasc Surg. 2021;71:338-345.
75.
TibautMCaprndaMKubatkaP, et al.Markers of atherosclerosis: Part 1 - serological markers. Heart Lung Circ. 2019;28:667-677.
76.
TibautMCaprndaMKubatkaP, et al.Markers of atherosclerosis: Part 2 - genetic and imaging markers. Heart Lung Circ. 2019;28:678-689.
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