Advertisement
Research Article| Volume 25, ISSUE 6, P1360-1365, June 2016

Apolipoprotein A-I and Paraoxonase-1 Are Potential Blood Biomarkers for Ischemic Stroke Diagnosis

      Background

      Blood biomarkers for ischemic and hemorrhagic stroke diagnosis remain elusive. Recent investigations suggested that apolipoprotein (Apo), matrix metalloproteinase (MMP), and paraoxonase-1 may be associated with stroke. We hypothesized that Apo A-I, Apo C-I, Apo C-III, MMP-3, MMP-9, and paraoxonase-1 are differentially expressed in ischemic stroke, hemorrhagic stroke, and controls.

      Methods

      In a single-center prospective observational study, consecutive stroke cases were enrolled if blood samples were obtainable within 12 hours of symptom onset. Age- (±5 years), race-, and sex-matched controls were recruited. Multiplex assays were used to measure protein levels. The Wilcoxon signed-rank test and the Mann–Whitney U-test were used to compare biomarker values between ischemic stroke patients and controls, hemorrhagic stroke patients and controls, and ischemic and hemorrhagic stroke patients. The 95% confidence intervals (CIs) for the difference of 2 medians were calculated.

      Results

      Fourteen ischemic stroke case–control pairs and 23 intracerebral hemorrhage (ICH) case–control pairs were enrolled. Median Apo A-I levels were lower in ischemic stroke cases versus controls (140 mg/dL versus 175 mg/dL, difference of 35 mg/dL, 95% CI −54 to −16) and in ischemic stroke versus ICH cases (140 mg/dL versus 180 mg/dL, difference of 40 mg/dL, 95% CI −57 to −23). Median paraoxonase-1 was lower in ischemic stroke cases than in both ICH cases and matched controls. Median Apo C-I was slightly lower in ischemic stroke cases than in ICH cases. There were no differences between groups for MMP-3, MMP-9, and Apo C-III.

      Conclusion

      Apo A-I and paraoxonase-1 levels may be clinically useful for ischemic stroke diagnosis and for differentiating between ischemic and hemorrhagic strokes.

      Key Words

      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:

      Subscribe to Journal of Stroke and Cerebrovascular Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Mozaffarian D.
        • Benjamin E.J.
        • Go A.S.
        • et al.
        Heart disease and stroke statistics—2015 update: a report from the American Heart Association.
        Circulation. 2015; 131: e29-e322
        • Nor A.M.
        • Davis J.
        • Sen B.
        • et al.
        The Recognition of Stroke in the Emergency Room (ROSIER) scale: development and validation of a stroke recognition instrument.
        Lancet Neurol. 2005; 4: 727-734
        • Lever N.M.
        • Nystrom K.V.
        • Schindler J.L.
        • et al.
        Missed opportunities for recognition of ischemic stroke in the emergency department.
        J Emerg Nurs. 2013; 39: 434-439
        • Adeoye O.
        • Albright K.C.
        • Carr B.G.
        • et al.
        Geographic access to acute stroke care in the United States.
        Stroke. 2014; 45: 3019-3024
        • Kodali P.
        • Chitta K.R.
        • Landero Figueroa J.A.
        • et al.
        Detection of metals and metalloproteins in the plasma of stroke patients by mass spectrometry methods.
        Metallomics. 2012; 4: 1077-1087
        • Ranade K.
        • Kirchgessner T.G.
        • Iakoubova O.A.
        • et al.
        Evaluation of the paraoxonases as candidate genes for stroke: Gln192Arg polymorphism in the paraoxonase 1 gene is associated with increased risk of stroke.
        Stroke. 2005; 36: 2346-2350
        • Kim N.S.
        • Kang K.
        • Cha M.H.
        • et al.
        Decreased paraoxonase-1 activity is a risk factor for ischemic stroke in Koreans.
        Biochem Biophys Res Commun. 2007; 364: 157-162
        • Kim E.M.
        • Hwang O.
        Role of matrix metalloproteinase-3 in neurodegeneration.
        J Neurochem. 2011; 116: 22-32
        • Kim S.K.
        • Kang S.W.
        • Kim D.H.
        • et al.
        Matrix metalloproteinase-3 gene polymorphisms are associated with ischemic stroke.
        J Interferon Cytokine Res. 2012; 32: 81-86
        • Gurney K.J.
        • Estrada E.Y.
        • Rosenberg G.A.
        Blood-brain barrier disruption by stromelysin-1 facilitates neutrophil infiltration in neuroinflammation.
        Neurobiol Dis. 2006; 23: 87-96
        • Cuadrado E.
        • Rosell A.
        • Penalba A.
        • et al.
        Vascular MMP-9/TIMP-2 and neuronal MMP-10 up-regulation in human brain after stroke: a combined laser microdissection and protein array study.
        J Proteome Res. 2009; 8: 3191-3197
        • Clark A.W.
        • Krekoski C.A.
        • Bou S.S.
        • et al.
        Increased gelatinase A (MMP-2) and gelatinase B (MMP-9) activities in human brain after focal ischemia.
        Neurosci Lett. 1997; 238: 53-56
        • Castellanos M.
        • Leira R.
        • Serena J.
        • et al.
        Plasma metalloproteinase-9 concentration predicts hemorrhagic transformation in acute ischemic stroke.
        Stroke. 2003; 34: 40-46
        • Allard L.
        • Lescuyer P.
        • Burgess J.
        • et al.
        ApoC-I and ApoC-III as potential plasmatic markers to distinguish between ischemic and hemorrhagic stroke.
        Proteomics. 2004; 4: 2242-2251
        • Lopez M.F.
        • Sarracino D.A.
        • Prakash A.
        • et al.
        Discrimination of ischemic and hemorrhagic strokes using a multiplexed, mass spectrometry-based assay for serum apolipoproteins coupled to multi-marker ROC algorithm.
        Proteomics Clin Appl. 2012; 6: 190-200
        • As S.
        • Sahukar S.
        • Murthy J.
        • et al.
        A study of serum apolipoprotein A1, apolipoprotein B and lipid profile in stroke.
        J Clin Diagn Res. 2013; 7: 1303-1306
        • Bonett D.G.
        • Price R.M.
        Statistical inference for a linear function of medians: confidence intervals, hypothesis testing, and sample size requirements.
        Psychol Methods. 2002; 7: 370-383
        • Eklund A.
        The bee swarm plot, an alternative to stripchart.
        (R Package Version 0.1.6)2013
        • Walldius G.
        • Jungner I.
        Apolipoprotein A-I versus HDL cholesterol in the prediction of risk for myocardial infarction and stroke.
        Curr Opin Cardiol. 2007; 22: 359-367
        • Walldius G.
        • Aastveit A.H.
        • Jungner I.
        Stroke mortality and the apoB/apoA-I ratio: results of the AMORIS prospective study.
        J Intern Med. 2006; 259: 259-266
        • Koren-Morag N.
        • Goldbourt U.
        • Graff E.
        • et al.
        Apolipoproteins B and AI and the risk of ischemic cerebrovascular events in patients with pre-existing atherothrombotic disease.
        J Neurol Sci. 2008; 270: 82-87
        • Bjorkegren J.
        Dual roles of apolipoprotein CI in the formation of atherogenic remnants.
        Curr Atheroscler Rep. 2006; 8: 1-2
        • Barter P.J.
        • Nicholls S.
        • Rye K.A.
        • et al.
        Antiinflammatory properties of HDL.
        Circ Res. 2004; 95: 764-772
        • Korita I.
        • Bulo A.
        • Langlois M.R.
        • et al.
        Serum amyloid A is independently related to apolipoprotein A-I but not to HDL-cholesterol in patients with angina pectoris.
        Clin Biochem. 2013; 46: 1660-1663
        • Wang D.X.
        • Liu H.
        • Yan L.R.
        • et al.
        The relationship between serum amyloid A and apolipoprotein A-I in high-density lipoprotein isolated from patients with coronary heart disease.
        Chin Med J. 2013; 126: 3656-3661
        • Pussinen P.J.
        • Malle E.
        • Metso J.
        • et al.
        Acute-phase HDL in phospholipid transfer protein (PLTP)-mediated HDL conversion.
        Atherosclerosis. 2001; 155: 297-305
        • Chen S.
        • Yang Q.
        • Chen G.
        • et al.
        An update on inflammation in the acute phase of intracerebral hemorrhage.
        Transl Stroke Res. 2015; 6: 4-8
        • Klebe D.
        • McBride D.
        • Flores J.J.
        • et al.
        Modulating the immune response towards a neuroregenerative peri-injury milieu after cerebral hemorrhage.
        J Neuroimmune Pharmacol. 2015; 10: 576-586
        • Coull B.
        Inflammation and stroke introduction.
        Stroke. 2007; 38: 631
        • Lindsberg P.J.
        • Grau A.J.
        Inflammation and infections as risk factors for ischemic stroke.
        Stroke. 2003; 34: 2518-2532
        • Dziedzic T.
        Systemic inflammation as a therapeutic target in acute ischemic stroke.
        Expert Rev Neurother. 2015; 15: 523-531
        • Furlong C.E.
        • Suzuki S.M.
        • Stevens R.C.
        • et al.
        Human PON1, a biomarker of risk of disease and exposure.
        Chem Biol Interact. 2010; 187: 355-361
        • Movva R.
        • Rader D.J.
        Laboratory assessment of HDL heterogeneity and function.
        Clin Chem. 2008; 54: 788-800