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, P. E. Norman, J. Golledge

    Research output: Contribution to journalArticlepeer-review

    7 Citations (Scopus)

    Abstract

    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 communitydwelling 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 mg/mL [interquartile range {IQR} (3.39-5.96)] and 4.43 mg/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 < .01). In vitro LRP1 blockade significantly reduced the ability of vascular smooth muscle cells to internalize extracellular MMP9. Conclusions: These data suggest that aortic but not circulating LRP1 is downregulated in patients with AAA and indicates a possible role for this protein in clearing an aneurysm-relevant ligand.
    Original languageEnglish
    Pages (from-to)466-473
    Number of pages8
    JournalEuropean Journal of Vascular and Endovascular Surgery
    Volume50
    Issue number4
    DOIs
    Publication statusPublished - 2015

    Keywords

    • aortic aneurysms
    • biomarkers
    • lipoproteins

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