Plasma Low-density Lipoprotein Receptor-related Protein 1 Concentration is not Associated with Human Abdominal Aortic Aneurysm Presence

J.V. Moxon, R. Behl-Gilhotra, S.K. Morton, S.M. Krishna, S.W. Seto, E. Biros, M. Nataatmadja, M. West, P.J. Walker, Paul Norman, J. Golledge

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    Abstract

    © 2015 Published by Elsevier Ltd on behalf of European Society for Vascular Surgery. All rights reserved. Objective/Background Recent genetic data suggest that a polymorphism of LRP1 is an independent risk factor for abdominal aortic aneurysm (AAA). The aims of this study were to assess whether plasma and aortic concentrations of low-density lipoprotein receptor-related protein 1 (LRP1) are associated with AAA, and to investigate the possible relevance of LRP1 to AAA pathophysiology. Methods Three analyses were conducted. First, plasma LRP1 concentrations were measured in community-dwelling men with and without AAA (n = 189 and n = 309, respectively) using enzyme-linked immunosorbent assay. Second, Western blotting analyses were employed to compare the expression of LRP1 protein in aortic biopsies collected from patients with AAA and nonaneurysmal postmortem donors (n = 6/group). Finally, the effect of in vitro LRP1 blockade on matrix metalloprotease 9 (MMP9) clearance by vascular smooth muscle cells was assessed by zymography. Results Plasma LRP1 concentrations did not differ between groups of men with and without AAA (median concentration 4.56 μg/mL [interquartile range {IQR} (3.39-5.96)] and 4.43 μg/mL [IQR 3.44-5.84], respectively; p =.48), and were not associated with AAA after adjusting for other risk factors (odds ratio 1.10 [95% confidence interval: 0.91-1.32]; p = 0.35). In contrast, LRP1 expression was approximately 3.4-fold lower in aortic biopsies recovered from patients with AAA compared with controls (median [IQR] expression 1.72 [0.94-3.14] and 5.91 [4.63-6.94] relative density units, respectively; p
    Original languageEnglish
    Pages (from-to)466-473
    Number of pages8
    JournalEuropean Journal of Vascular and Endovascular Surgery
    Volume50
    Issue number4
    Early online date16 Jul 2015
    DOIs
    Publication statusPublished - Oct 2015

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