Moxon, Joseph V., Behl-Gilhotra, Ratnesh, Morton, Susan K., Krishna, Smriti M., Seto, Sai Wang, Biros, Erik, Nataatmadja, Maria, West, Malcolm, Walker, Phillip J., Norman, Paul E., and Golledge, Jonathan (2015) Plasma low-density lipoprotein receptor-related protein 1 concentration is not associated with human abdominal aortic aneurysm presence. European Journal of Vascular and Endovascular Surgery, 50 (4). pp. 466-473.

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Abstract

Objectives: Recent genetic data suggest that a polymorphism of the low density lipoprotein receptor-related protein 1 (LRP1) gene is an independent risk factor for abdominal aortic aneurysm. The aims of this study were to assess whether plasma and aortic concentrations of LRP1 were associated with abdominal aortic aneurysm, and to investigate the possible relevance of LRP1 to abdominal aortic aneurysm pathophysiology.

Design, Materials and Methods: Three analyses were conducted. Initially, plasma LRP1 concentrations were measured in community dwelling men with and without abdominal aortic aneurysm (n=189 and 309 respectively) using ELISA. Secondly, Western blotting analyses were employed to compare the expression of LRP1 protein in aortic biopsies collected from abdominal aortic aneurysm patients and non-aneurysmal post-mortem donors (n=6/group). Finally, the effect of in vitro LRP1 blockade on 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 abdominal aortic aneurysm (median concentration 4.56 µg/mL (IQR 3.39-5.96) and 4.43 µg/mL (IQR 3.44-5.84); P=0.48), and were not associated with abdominal aortic aneurysm 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 ~3.4 fold lower in aortic biopsies recovered from abdominal aortic aneurysm patients compared to controls (median (IQR) expression 1.72 (0.94-3.14) and 5.91 (4.63-6.94) relative density units; P=0.004). In vitro LRP1 blockade significantly reduced the ability of vascular smooth muscle cells to internalise extracellular MMP9.

Conclusions: These data suggest that aortic but not circulating LRP1 is down-regulated in abdominal aortic aneurysm patients, and indicates a possible role for this protein in clearing an aneurysm-relevant ligand.

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