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

doi:10.1016/j.ejvs.2015.06.023

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

Eur J Vasc Endovasc Surg. 2015 Oct;50(4):466-73. doi: 10.1016/j.ejvs.2015.06.023. Epub 2015 Jul 16.

Authors

J V Moxon¹, R Behl-Gilhotra¹, S K Morton¹, S M Krishna¹, S W Seto², E Biros¹, M Nataatmadja³, M West³, P J Walker⁴, P E Norman⁵, J Golledge⁶

Affiliations

¹ Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia.
² Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia; National Institute of Complementary Medicine, University of Western Sydney, Campbelltown, NSW 2560, Australia.
³ The Cardiovascular Research Group, Department of Medicine, University of Queensland, The Prince Charles Hospital, Brisbane, QLD 4032, Australia.
⁴ School of Medicine, Discipline of Surgery and Centre for Clinical Research, University of Queensland, Herston, QLD 4072, Australia.
⁵ School of Surgery, University of Western Australia, Perth, WA 6009, Australia.
⁶ Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia; School of Medicine, Discipline of Surgery and Centre for Clinical Research, University of Queensland, Herston, QLD 4072, Australia; Department of Vascular and Endovascular Surgery, The Townsville Hospital, Townsville, QLD 4814, Australia. Electronic address: [email protected].

PMID: 26188720
DOI: 10.1016/j.ejvs.2015.06.023

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 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 < .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.

Keywords: Abdominal aortic aneurysm; Biomarker; Low-density lipoprotein receptor-related protein-1; Matrix metalloprotease 9.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Antibodies / pharmacology
Aorta, Abdominal / drug effects
Aorta, Abdominal / metabolism*
Aortic Aneurysm, Abdominal / blood*
Aortic Aneurysm, Abdominal / diagnosis
Biomarkers / blood
Biopsy
Blotting, Western
Case-Control Studies
Cells, Cultured
Down-Regulation
Enzyme-Linked Immunosorbent Assay
Humans
Low Density Lipoprotein Receptor-Related Protein-1 / antagonists & inhibitors
Low Density Lipoprotein Receptor-Related Protein-1 / blood*
Male
Matrix Metalloproteinase 9 / metabolism
Muscle, Smooth, Vascular / metabolism
Myocytes, Smooth Muscle / metabolism
Odds Ratio
Risk Factors

Substances

Antibodies
Biomarkers
LRP1 protein, human
Low Density Lipoprotein Receptor-Related Protein-1
MMP9 protein, human
Matrix Metalloproteinase 9