In-Stent Stenosis: Potential Role of Increased Oxidative Stress and Glutathione-Linked Detoxification Mechanisms

Misra, Praphul; Reddy, Pratap; Shukla, Deepti; Caldito, Gloria; Yerra, Lakshminarayan; Aw, Tak Yee

doi:10.1177/0003319707309651

Cited by 13 publications

(16 citation statements)

References 25 publications

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“…In previous studies, significant results were obtained concerning GPx, but the participating groups were usually chosen among sportsmen, healthy people or CAD patients but not from an intermediate group (23,24). In concordance with our study, the association between CAD and the increase or decrease of basal GPx levels is examined (10)(11)25). In a previous study evaluating syndrome X and SOD activity it is shown that the increased SOD activity would reduce complaints and increase the quality of life in patients with syndrome X (22,26).…”

Section: Discussionsupporting

confidence: 80%

See 1 more Smart Citation

The effect of antioxidant enzyme levels and exercise on syndrome X and coronary slow flow phenomenon: an observational study

Kaplan¹,

Meriç²,

Acar³

et al. 2013

Anadolu Kardiyol Derg

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Objective: In this study the antioxidant enzyme [catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) ] levels at rest in patients with syndrome X and coronary slow flow are measured. Then it has been investigated whether there is any enzymatic difference between the normal controls and syndrome X patients or patients with coronary slow flow and ascertain if exercise has any effects on the antioxidant enzyme levels. Methods: Fifty-five patients were included in this prospective observational controlled study. Patients were divided into 3 groups: Group 1-normal controls (n=20); Group 2-patients with coronary slow flow (n=20); and Group 3-patients diagnosed with syndrome X (n=15). In all patients, blood samples were collected at rest and after maximal exercise. The antioxidant enzymes (SOD, CAT, Gpx) in the erythrocytes were studied for these three groups of blood sample. Statistical analysis was performed using Student t-test, Mann-Whitney U and Chi-square tests, KruskalWallis variance analysis and ANOVA. Results: Under basal conditions the lowest SOD and GPx levels were measured in the 2 nd Group, whereas significant differences in paired comparisons were observed only between the 2 nd and 3 rd Groups (p=0.024 vs. p<0.01, respectively) during paired comparisons. The postexercise SOD levels were decreased significantly in the 3 rd Groups when compared with the basal concentrations (p=0.014), however no significant pre-and post-exercise differences were observed in the CAT and GPx concentrations (p>0.05). Conclusion: The post-exercise SOD level when compared with basal SOD levels were decreased significantly in the syndrome X group, however no differences were observed between the other groups. This can be interpreted as the reduction in the exercise related symptoms and ischemic findings are resulting from the decrease of SOD activity. (Anadolu Kardiyol Derg 2013; 13: 641-6) Key words: Coronary slow flow, syndrome X, antioxidant enzymes Original Investigation Özgün Araşt›rma 641ÖZET Amaç: Bu çalışmada, sendrom X ve yavaş koroner akım hastalarında istirahatte antioksidan enzim [katalaz (CAT), süperoksid dismutaz (SOD) ve glutatyon peroksidaz (GPx)] düzeyleri ölçülerek normal kontrollerle fark gösterip göstermediği, egzersizin enzim düzeylerine etkisi olup olmadı-ğı araştırılmak istenmiştir.Yöntemler: Prospektif kontrollü gözlemsel bu çalışmaya 55 kişi alındı. Hastalar, normal kontroller (Grup 1, n= 20), koroner yavaş akımı olan hastalar (Grup 2, n=20) ve Sendrom X tanısı konan hastalar (Grup 3, n=15) olmak üzere 3 gruba ayrıldı. Tüm hastalardan istirahatte ve maksimum efor sonrası kanlar alındı ve eritrosit içindeki antioksidan enzimler (SOD, CAT, GPx) çalışıldı. İstatistiksel analiz Student t-testi, Mann-Whitney U, Ki-kare testi, Kruskal-Wallis varyans analizi ve ANOVA (post-hoc) kullanılarak yapıldı. Bulgular: Bazal şartlarda ölçülen SOD ve GPx değerleri en düşük olarak Grup 2'de saptanırken, ikili karşılaştırmada yalnızca Grup 2 ve 3 arasın-da anlamlı fark vardı (p sırasıyla 0,02...

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Section: Discussionsupporting

confidence: 80%

“…It has been thought that, slow coronary flow and syndrome X are part of this process (2)(3)(4)(5)(6)(7)(8)(9). The relation between oxidant enzyme level and coronary artery disease has been revealed by previous studies (10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 94%

The effect of antioxidant enzyme levels and exercise on syndrome X and coronary slow flow phenomenon: an observational study

Kaplan¹,

Meriç²,

Acar³

et al. 2013

Anadolu Kardiyol Derg

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“…In combination with this magnetic guidance strategy, antioxidant enzyme-loaded MNP whose efficacy has been demonstrated in the present study may be an interesting candidate for a stent-targeted antirestenotic therapy. A rationale for exploring the potential of antioxidant enzymes, SOD and catalase, either alone or in combination, for preventing restenosis is based on the major contribution of ROS to the cascade of events eventually resulting in the vessel reobstruction [36, 37], with a proof-of-concept provided in previous studies using gene vectors encoding these proteins [38, 39]. …”

Section: Discussionmentioning

confidence: 99%

Endothelial delivery of antioxidant enzymes loaded into non-polymeric magnetic nanoparticles

Chorny

Hood

Levy

et al. 2010

Journal of Controlled Release

106

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Antioxidant enzymes have shown promise as a therapy for pathological conditions involving increased production of reactive oxygen species (ROS). However the efficiency of their use for combating oxidative stress is dependent on the ability to achieve therapeutically adequate levels of active enzymes at the site of ROS-mediated injury. Thus, the implementation of antioxidant enzyme therapy requires a strategy enabling both guided delivery to the target site and effective protection of the protein in its active form. To address these requirements we developed magnetically responsive nanoparticles (MNP) formed by precipitation of calcium oleate in the presence of magnetite-based ferrofluid (controlled aggregation/precipitation) as a carrier for magnetically guided delivery of therapeutic proteins. We hypothesized that antioxidant enzymes, catalase and superoxide dismutase, can be protected from proteolytic inactivation by encapsulation in MNP. We also hypothesized that catalase-loaded MNP applied with a high-gradient magnetic field can rescue endothelial cells from hydrogen peroxide toxicity in culture. To test these hypotheses, a family of enzyme-loaded MNP formulations were prepared and characterized with respect to their magnetic properties, enzyme entrapment yields and protection capacity. SOD-and catalase-loaded MNP were formed with average sizes ranging from 300 to 400 nm, and a protein loading efficiency of 20-33%. MNP were strongly magnetically responsive (magnetic moment at saturation of 14.3 emu/g) in the absence of magnetic remanence, and exhibited a protracted release of their cargo protein in plasma. Catalase stably associated with MNP was protected from proteolysis and retained 20% of its initial enzymatic activity after 24 hr of exposure to pronase. Under magnetic guidance catalase-loaded MNP were rapidly taken up by cultured endothelial cells providing increased resistance to oxidative stress (62±12% cells rescued from hydrogen peroxide induced cell death vs. 10±4% under non-magnetic conditions). We conclude that non-polymeric MNP formed using the controlled aggregation/precipitation strategy are a promising carrier for targeted antioxidant enzyme therapy, and in combination with magnetic guidance can be applied to protect endothelial cells from oxidative stress mediated damage. This protective effect of

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“…ISR and metal ions are both known to stimulate increased oxidative stress and a reduction in anti-oxidant enzymes [37]. VSMCs treated with SS ions were measured for the generation of hydrogen peroxide (H 2 O 2 ).…”

Section: Resultsmentioning

confidence: 99%

Stainless Steel Ions Stimulate Increased Thrombospondin-1-Dependent TGF-Beta Activation by Vascular Smooth Muscle Cells: Implications for In-Stent Restenosis

Pallero

Roden²,

Chen³

et al. 2009

J Vasc Res

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Background/Aims: Despite advances in stent design, in-stent restenosis (ISR) remains a significant clinical problem. All implant metals exhibit corrosion, which results in release of metal ions. Stainless steel (SS), a metal alloy widely used in stents, releases ions to the vessel wall and induces reactive oxygen species, inflammation and fibroproliferative responses. The molecular mechanisms are unknown. TGF-β is known to be involved in the fibroproliferative responses of vascular smooth muscle cells (VSMCs) in restenosis, and TGF-β antagonists attenuate ISR. We hypothesized that SS ions induce the latent TGF-β activator, thrombospondin-1 (TSP1), through altered oxidative signaling to stimulate increased TGF-β activation and VSMC phenotype change. Methods: VSMCs were treated with SS metal ion cocktails, and morphology, TSP1, extracellular matrix production, desmin and TGF-β activity were assessed by immunoblotting. Results: SS ions stimulate the synthetic phenotype, increased TGF-β activity, TSP1, increased extracellular matrix and downregulation of desmin in VSMCs. Furthermore, SS ions increase hydrogen peroxide and decrease cGMP-dependent protein kinase (PKG) signaling, a known repressor of TSP1 transcription. Catalase blocks SS ion attenuation of PKG signaling and increased TSP1 expression. Conclusions: These data suggest that ions from stent alloy corrosion contribute to ISR through stimulation of TSP1-dependent TGF-β activation.

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In-Stent Stenosis: Potential Role of Increased Oxidative Stress and Glutathione-Linked Detoxification Mechanisms

Cited by 13 publications

References 25 publications

The effect of antioxidant enzyme levels and exercise on syndrome X and coronary slow flow phenomenon: an observational study

The effect of antioxidant enzyme levels and exercise on syndrome X and coronary slow flow phenomenon: an observational study

Endothelial delivery of antioxidant enzymes loaded into non-polymeric magnetic nanoparticles

Stainless Steel Ions Stimulate Increased Thrombospondin-1-Dependent TGF-Beta Activation by Vascular Smooth Muscle Cells: Implications for In-Stent Restenosis

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