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Plasma 24-hydroxycholesterol is associated with narrower common carotid artery and greater flow velocities in relapsing multiple sclerosis

  • Dejan Jakimovski
    Correspondence
    Corresponding author.
    Affiliations
    Department of Neurology, Buffalo Neuroimaging Analysis Center (BNAC), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, 100 High Street, Buffalo, NY 14203, United States
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  • Robert Zivadinov
    Affiliations
    Department of Neurology, Buffalo Neuroimaging Analysis Center (BNAC), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, 100 High Street, Buffalo, NY 14203, United States

    Center for Biomedical Imaging at Clinical Translational Science Institute, University at Buffalo, State University of New York, Buffalo, NY, United States
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  • Laura Pelizzari
    Affiliations
    IRCCS, Fondazione Don Carlo Gnocchi, Milan, Italy
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  • Cynthia Dunne-Jaffe
    Affiliations
    Department of Neurology, Buffalo Neuroimaging Analysis Center (BNAC), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, 100 High Street, Buffalo, NY 14203, United States
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  • Richard W. Browne
    Affiliations
    Department of Biotechnical and Clinical Laboratory Sciences, State University of New York, Buffalo, NY, United States
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  • Niels Bergsland
    Affiliations
    Department of Neurology, Buffalo Neuroimaging Analysis Center (BNAC), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, 100 High Street, Buffalo, NY 14203, United States

    IRCCS, Fondazione Don Carlo Gnocchi, Milan, Italy
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  • Michael G. Dwyer
    Affiliations
    Department of Neurology, Buffalo Neuroimaging Analysis Center (BNAC), Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, 100 High Street, Buffalo, NY 14203, United States
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  • Bianca Weinstock-Guttman
    Affiliations
    Department of Neurology, Jacobs Comprehensive MS Treatment and Research Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, United States
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  • Murali Ramanathan
    Affiliations
    Department of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY, United States
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      Highlights

      • Oxidized cholesterol molecules (oxysterols) have been implicated in multiple sclerosis (MS).
      • The relationship between oxysterol and vascular pathology was investigated in 99 MS patients and 38 healthy controls.
      • Higher 24-hydroxycholesterol (HC) levels are associated with smaller lumen of the common carotid artery (CCA) in relapsing-remitting MS patients.
      • Higher 24HC levels were also associated with greater time-averaged and peak diastolic velocities.
      • Potent anti-inflammatory therapy may decrease the oxysterol levels in MS patients.

      Abstract

      Background

      Multiple sclerosis (MS) studies suggest greater cardiovascular disease burden and disturbances in the cholesterol pathways. The potential impact of oxidized cholesterol molecules on MS is emerging.

      Objective

      To determine the relationship between multiple oxysterol molecules and atherosclerosis burden in MS patients.

      Materials and Methods

      A total of 99 MS patients (61 relapsing-remitting MS(RRMS) and 38 progressive MS (PMS)) patients and 38 healthy controls (HCs) underwent magnetic resonance angiography (MRA) and the cross-sectional area (CSA) of the common carotid artery (CCA) was determined at three different levels before the bifurcation (C7, C6 and C5). Additionally, an echo-color Doppler ultrasound was performed and measures of blood flow velocities were derived. Blood samples acquired at the time of the imaging examinations were analyzed and 24-, 25-, 27-hydroxycholesterol (24HC, 25HC, 27HC) and 7-ketocholesterol (7KC) were quantified in ng/mL

      Results

      In the MS patients, higher levels of 24HC were significantly associated with smaller CCA CSA measured at all three cervical levels (r=-0.201, p = 0.046; r=-0.228, p = 0.023, and r=-0.215, p = 0.032, for C7, C6 and C5, respectively). These associations were driven by the RRMS group only (r=-0.407, p = 0.002 for C7; r=-0.414, p = 0.002, for C6; and r=-0.368, p = 0.006 for C5). No associations were seen in the HCs. Despite adjusting for the significant age effect (B = 0.445, p = 0.004), higher 24HC levels were independently associated with smaller CCA CSA (B=-0.20, p = 0.045). 24HC was additionally associated with greater time-averaged and peak diastolic CCA velocities. RRMS patients treated with potent anti-inflammatory therapies had lower oxysterol levels (p = 0.019).

      Conclusion

      Greater 24HC levels are associated with smaller CSA CCA and greater flow velocities in RRMS patients.

      Keywords

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