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  • Ovid Technologies (Wolters Kluwer Health)  (2)
  • 1
    Online Resource
    Online Resource
    Mechanistic Insights Into Nitrite-Induced Cardioprotection Using an Integrated Metabolomic/Proteomic Approach
    Ovid Technologies (Wolters Kluwer Health) ; 2009
    In:  Circulation Research Vol. 104, No. 6 ( 2009-03-27), p. 796-804
    Details
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 104, No. 6 ( 2009-03-27), p. 796-804
    Abstract: Nitrite has recently emerged as an important bioactive molecule, capable of conferring cardioprotection and a variety of other benefits in the cardiovascular system and elsewhere. The mechanisms by which it accomplishes these functions remain largely unclear. To characterize the dose response and corresponding cardiac sequelae of transient systemic elevations of nitrite, we assessed the time course of oxidation/nitros(yl)ation, as well as the metabolomic, proteomic, and associated functional changes in rat hearts following acute exposure to nitrite in vivo. Transient systemic nitrite elevations resulted in: (1) rapid formation of nitroso and nitrosyl species; (2) moderate short-term changes in cardiac redox status; (3) a pronounced increase in selective manifestations of long-term oxidative stress as evidenced by cardiac ascorbate oxidation, persisting long after changes in nitrite-related metabolites had normalized; (4) lasting reductions in glutathione oxidation (GSSG/GSH) and remarkably concordant nitrite-induced cardioprotection, which both followed a complex dose–response profile; and (5) significant nitrite-induced protein modifications (including phosphorylation) revealed by mass spectrometry-based proteomic studies. Altered proteins included those involved in metabolism (eg, aldehyde dehydrogenase 2, ubiquinone biosynthesis protein CoQ9, lactate dehydrogenase B), redox regulation (eg, protein disulfide isomerase A3), contractile function (eg, filamin-C), and serine/threonine kinase signaling (eg, protein kinase A R1α, protein phosphatase 2A A R1-α). Thus, brief elevations in plasma nitrite trigger a concerted cardioprotective response characterized by persistent changes in cardiac metabolism, redox stress, and alterations in myocardial signaling. These findings help elucidate possible mechanisms of nitrite-induced cardioprotection and have implications for nitrite dosing in therapeutic regimens.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    URL: Article
    DOI: 10.1161/CIRCRESAHA.108.187005
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2009
    detail.hit.zdb_id: 1467838-X
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  • 2
    Online Resource
    Online Resource
    C-Reactive Protein as a Prognostic Marker After Lacunar Stroke : Levels of Inflammatory Markers in the Treatment of Stroke Study
    Ovid Technologies (Wolters Kluwer Health) ; 2014
    In:  Stroke Vol. 45, No. 3 ( 2014-03), p. 707-716
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 45, No. 3 ( 2014-03), p. 707-716
    Abstract: Inflammatory biomarkers predict incident and recurrent cardiac events, but their relationship to stroke prognosis is uncertain. We hypothesized that high-sensitivity C-reactive protein (hsCRP) predicts recurrent ischemic stroke after recent lacunar stroke. Methods— Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) was an international, multicenter, prospective ancillary biomarker study nested within Secondary Prevention of Small Subcortical Strokes (SPS3), a phase III trial in patients with recent lacunar stroke. Patients were assigned in factorial design to aspirin versus aspirin plus clopidogrel, and higher versus lower blood pressure targets. Patients had blood samples collected at enrollment and hsCRP measured using nephelometry at a central laboratory. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for recurrence risks before and after adjusting for demographics, comorbidities, and statin use. Results— Among 1244 patients with lacunar stroke (mean age, 63.3±10.8 years), median hsCRP was 2.16 mg/L. There were 83 recurrent ischemic strokes (including 45 lacunes) and 115 major vascular events (stroke, myocardial infarction, and vascular death). Compared with the bottom quartile, those in the top quartile (hsCRP 〉 4.86 mg/L) were at increased risk of recurrent ischemic stroke (unadjusted HR, 2.54; 95% CI, 1.30–4.96), even after adjusting for demographics and risk factors (adjusted HR, 2.32; 95% CI, 1.15–4.68). hsCRP predicted increased risk of major vascular events (top quartile adjusted HR, 2.04; 95% CI, 1.14–3.67). There was no interaction with randomized antiplatelet treatment. Conclusions— Among recent lacunar stroke patients, hsCRP levels predict the risk of recurrent strokes and other vascular events. hsCRP did not predict the response to dual antiplatelets. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00059306.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.113.004562
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2014
    detail.hit.zdb_id: 1467823-8
    Location Call Number Limitation Availability
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