Clinical Application of NOX Activity and Other Oxidative Biomarkers in Cardiovascular Disease: A Critical Review

Violi, Francesco; Pignatelli, Pasquale

doi:10.1089/ars.2013.5790

Cited by 36 publications

(38 citation statements)

References 155 publications

(189 reference statements)

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“…Oxidative stress plays a pivotal role in the pathogenesis of vascular disease (24). The activity of vascular NADPH oxidase, a major source of O 2 _ 2 , is increased in patients with type 2 diabetes (2,25,26), a finding replicated in our cohort.…”

Section: Discussionsupporting

confidence: 75%

Adiponectin as a Link Between Type 2 Diabetes and Vascular NADPH Oxidase Activity in the Human Arterial Wall: The Regulatory Role of Perivascular Adipose Tissue

et al. 2014

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Oxidative stress plays a critical role in the vascular complications of type 2 diabetes. We examined the effect of type 2 diabetes on NADPH oxidase in human vessels and explored the mechanisms of this interaction. Segments of internal mammary arteries (IMAs) with their perivascular adipose tissue (PVAT) and thoracic adipose tissue were obtained from 386 patients undergoing coronary bypass surgery (127 with type 2 diabetes). Type 2 diabetes was strongly correlated with hypoadiponectinemia and increased vascular NADPH oxidase-derived superoxide anions (O 2 _ 2 ). The genetic variability of the ADIPOQ gene and circulating adiponectin (but not interleukin-6) were independent predictors of NADPH oxidasederived O 2 _ 2 . However, adiponectin expression in PVAT was positively correlated with vascular NADPH oxidasederived O 2 _ 2 . Recombinant adiponectin directly inhibited NADPH oxidase in human arteries ex vivo by preventing the activation/membrane translocation of Rac1 and downregulating p22 phox through a phosphoinositide 3-kinase/Akt-mediated mechanism. In ex vivo coincubation models of IMA/PVAT, the activation of arterial NADPH oxidase triggered a peroxisome proliferator-activated receptor-g-mediated upregulation of the adiponectin gene in the neighboring PVAT via the release of vascular oxidation products. We demonstrate for the first time in humans that reduced adiponectin levels in individuals with type 2 diabetes stimulates vascular NADPH oxidase, while PVAT "senses" the increased NADPH oxidase activity in the underlying vessel and responds by upregulating adiponectin gene expression. This PVAT-vessel interaction is identified as a novel therapeutic target for the prevention of vascular complications of type 2 diabetes.

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Section: Discussionsupporting

confidence: 75%

Adiponectin as a Link Between Type 2 Diabetes and Vascular NADPH Oxidase Activity in the Human Arterial Wall: The Regulatory Role of Perivascular Adipose Tissue

et al. 2014

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“…In fact, the reduction of IL-10 has been described as a pro-atherogenic inflammatory condition [34] whereas hs-CRP is not a universal predictor of CV risk [35] and its levels are strictly related to IL-6 rather than other cytokines production [36]. Our data also showed a significant increase of ox-LDL levels in the nilotinib cohort of patients; this may not be due to higher circulating LDL levels but to an increased pro-oxidative, inflammatory- and genetically-driven state [37]. The finding of an increased ox-LDL level is of interest because it is independently associated with atherothrombotic events, regardless of classical parameters of lipid profile.…”

Section: Discussionmentioning

confidence: 76%

Genetic predisposition and induced pro-inflammatory/pro-oxidative status may play a role in increased atherothrombotic events in nilotinib treated chronic myeloid leukemia patients

et al. 2016

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Several reports described an increased risk of cardiovascular (CV) events, mainly atherothrombotic, in Chronic Myeloid Leukemia (CML) patients receiving nilotinib. However, the underlying mechanism remains elusive. The objective of the current cross-sectional retrospective study is to address a potential correlation between Tyrosine Kinase Inhibitors (TKIs) treatment and CV events. One hundred and 10 chronic phase CML patients in complete cytogenetic response during nilotinib or imatinib, were screened for CV events and evaluated for: traditional CV risk factors, pro/anti-inflammatory biochemical parameters and detrimental ORL1 gene polymorphisms (encoding for altered oxidized LDL receptor-1). Multivariate analysis of the whole cohort showed that the cluster of co-existing nilotinib treatment, dyslipidaemia and G allele of LOX-1 polymorphism was the only significant finding associated with CV events. Furthermore, multivariate analysis according to TKI treatment confirmed IVS4-14 G/G LOX-1 polymorphism as the strongest predictive factor for a higher incidence of CV events in nilotinib patients. Biochemical assessment showed an unbalanced pro-inflammatory cytokines network in nilotinib vs imatinib patients. Surprisingly, pre-existing traditional CV risk factors were not always predictive of CV events. We believe that in nilotinib patients an induced “inflammatory/oxidative status”, together with a genetic pro-atherothrombotic predisposition, may favour the increased incidence of CV events. Prospective studies focused on this issue are ongoing.

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“…A szuperoxid szabályozza a NO ér-tágító hatását. A fokozott NOX-aktivitás azonban kedvezőtlenül befolyásolja az ér szerkezetét: serkenti a vasocon strictiót, a thrombocytaaggregációt, valamint a szuperoxid-dizmutáz (SOD) által keletkező hidrogén-peroxid (H 2 O 2 ) önmagában is aktiválja a thrombocytá-kat [6]. A xantinoxidáz NADH, O 2 és xantin/hypoxantin felhasználásával termel szuperoxid aniont és H 2 O 2 -t. A fokozott XO-aktivitás rontja az endothelfüggő vasodilatatiót [5].…”

Section: Oxidatív Stressz Az Endothelbenunclassified

“…Az MPO aktivitása az érfal-ban negatívan érinti a gyulladás ellen védő mechanizmusokat: a NO inaktiválásához, LDL-oxidációhoz, a HDL gyulladásgátló tulajdonságának csökkenéséhez vezet. Az MPO a metalloproteinázok aktiválásán keresztül előse-gítheti a plakkdestabilizációt, -eróziót [6].…”

Section: Oxidatív Stressz Az Endothelbenunclassified

“…Az endothelen átjutott LDL a B100 apolipoproteinen keresztül kötődik az extracelluláris mátrix (ECM) proteo glikánjaihoz, majd a vascularis sejtek által enyhén oxidálódik [3,6]. A subintimalis ECM-ben csapdába esett LDL-részecskék stimulálják a vascularis sejtek ICAM-1, vascularis sejtadhéziós molekula-1 (VCAM-1), MCP-1, granulocyta-és macrophagkolónia-stimuláló faktorok termelését.…”

Section: Az Ldl-oxidáció Következményeiunclassified

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Oxidatív stressz és atherosclerosis

Stark

2015

Orvosi Hetilap

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Az atherosclerosis, ami a mai napig vezető halálok a fejlett országokban, genetikai hajlam és számos ismert környeze-ti rizikótényező hatására alakul ki. A legtöbb ilyen faktor oxidatív stressz keltése révén endothelialis működészavarhoz és egyéb proatherogen folyamatokhoz vezet. Az érelmeszesedés elsősorban az artériás rendszer tipikus helyein, az elágazásoknál és kanyarulatoknál alakul ki, ahol a szabályos lamináris áramlás zavart szenved. Emiatt fokozódik az endothelium permeabilitása a kis sűrűségű lipoprotein számára, ami így felhalmozódik az érfal intimarétegében és oxidálódik. Az oxidált kis sűrűségű lipoprotein számos úton hozzájárul az atherosclerosis kialakulásához: elősegíti a monocyták vándorlását az érfalba, a habossejt-képződést, a meszes plakk kialakulását, a plakkdestabilizációt és a thromboticus szövődményeket. Miután az oxidatív stressz az atherosclerosis patogenezisében számos ponton szerepet játszik, felmerül, hogy antioxidáns terápiával megelőzhető-e a betegség. Több klinikai vizsgálat szerint az antioxidánsok -mint az N-acetil-cisztein, C-és E-vitamin, folsav, ösztrogének -hatékonyak a coronariabetegség megelőzésében, de ezt randomizált klinikai vizsgálatok nem tudták bizonyítani. Orv. Hetil., 2015, 156(28), 1115-1119. Kulcsszavak: oxidatív stressz, érelmeszesedés, LDL-koleszterin, atheroscleroticus plakk, antioxidánsok Oxidative stress and atherosclerosisAtherosclerosis is a leading cause of death in developed countries. Genetic susceptibility and environmental factors play a role in the pathogenesis. Most of these factors lead to endothelial dysfunction and other pro-atherogenic processes by causing oxidative stress. Atherosclerosis typically develops at the curved and branched regions of the arterial tree, where the laminar blood fl ow is disturbed. This leads to increased permeability of the endothel to low density lipoprotein molecules, which accumulate in the intima and are oxidised by vascular cells. Oxidised low density lipoprotein takes part in many phases of atherogenesis: stimulates the binding of monocytes to the endothel, foam cell formation, the development of plaques, plaque destabilization and thrombotic complications. Since oxidative stress plays an important role in atherogenesis, it has been suggested that antioxidant molecules might have antiatherogenic function. Many clinical investigations have shown that antioxidants such as N-acetylcystein, vitamin E and C, folic acid, and estrogens can prevent atherosclerosis, however, randomized studies failed to confi rm this effect.Keywords: oxidative stress, atherosclerosis, LDL cholesterol, atherosclerotic plaque, antioxidants Stark, J. [Oxidative stress and atherosclerosis]. Orv. Hetil., 2015, 156(28), 1115-1119. (Beérkezett: 2015 elfogadva: 2015. május 22.) A közlemény a Fehér János Alapítvány pályázatán díjazott pályamunka. ÖSSZEFOGLALÓ KÖZLEMÉNYRövidítések ECM = extracelluláris mátrix; eNOS = endothelialis nitrogén-monoxid-szintáz; FGF = fi broblast növekedési faktor; ICAM-1 = intracelluláris adhéziós molekula-1; LOX-1...

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Clinical Application of NOX Activity and Other Oxidative Biomarkers in Cardiovascular Disease: A Critical Review

Cited by 36 publications

References 155 publications

Adiponectin as a Link Between Type 2 Diabetes and Vascular NADPH Oxidase Activity in the Human Arterial Wall: The Regulatory Role of Perivascular Adipose Tissue

Adiponectin as a Link Between Type 2 Diabetes and Vascular NADPH Oxidase Activity in the Human Arterial Wall: The Regulatory Role of Perivascular Adipose Tissue

Genetic predisposition and induced pro-inflammatory/pro-oxidative status may play a role in increased atherothrombotic events in nilotinib treated chronic myeloid leukemia patients

Oxidatív stressz és atherosclerosis

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