title: Plasma Low-density Lipoprotein Receptor-related Protein 1 Concentration is not Associated with Human Abdominal Aortic Aneurysm Presence.
abstract: OBJECTIVE
  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.
authors.affiliation: Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia.
authors.forename: J V
authors.initials: JV
authors.lastname: Moxon
authors.affiliation: Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Behl-Gilhotra
authors.affiliation: Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia.
authors.forename: S K
authors.initials: SK
authors.lastname: Morton
authors.affiliation: Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia.
authors.forename: S M
authors.initials: SM
authors.lastname: Krishna
authors.affiliation: 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.
authors.forename: S W
authors.initials: SW
authors.lastname: Seto
authors.affiliation: Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia.
authors.forename: E
authors.initials: E
authors.lastname: Biros
authors.affiliation: The Cardiovascular Research Group, Department of Medicine, University of Queensland, The Prince Charles Hospital, Brisbane, QLD 4032, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Nataatmadja
authors.affiliation: The Cardiovascular Research Group, Department of Medicine, University of Queensland, The Prince Charles Hospital, Brisbane, QLD 4032, Australia.
authors.forename: M
authors.initials: M
authors.lastname: West
authors.affiliation: School of Medicine, Discipline of Surgery and Centre for Clinical Research, University of Queensland, Herston, QLD 4072, Australia.
authors.forename: P J
authors.initials: PJ
authors.lastname: Walker
authors.affiliation: School of Surgery, University of Western Australia, Perth, WA 6009, Australia.
authors.forename: P E
authors.initials: PE
authors.lastname: Norman
authors.affiliation: 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: jonathan.golledge@jcu.edu.au.
authors.forename: J
authors.initials: J
authors.lastname: Golledge
mesh_terms: D000368:Aged; D000906:Antibodies / Q000494:pharmacology; D001012:Aorta, Abdominal / Q000187:drug effects / Q000378:metabolism*; D017544:Aortic Aneurysm, Abdominal / Q000097:blood* / Q000175:diagnosis; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D015153:Blotting, Western; D016022:Case-Control Studies; D002478:Cells, Cultured; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1 / Q000037:antagonists & inhibitors / Q000097:blood*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D016017:Odds Ratio; D012307:Risk Factors
chemical_list: D000906:Antibodies; D015415:Biomarkers; C475476:LRP1 protein, human; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: Abdominal aortic aneurysm; Biomarker; Low-density lipoprotein receptor-related protein-1; Matrix metalloprotease 9