title: Extracellular matrix composition and remodeling in human abdominal aortic aneurysms: a proteomics approach.
abstract: Abdominal aortic aneurysms (AAA) are characterized by pathological remodeling of the aortic extracellular matrix (ECM). However, besides the well-characterized elastolysis and collagenolysis little is known about changes in other ECM proteins. Previous proteomics studies on AAA focused on cellular changes without emphasis on the ECM. In the present study, ECM proteins and their degradation products were selectively extracted from aneurysmal and control aortas using a solubility-based subfractionation methodology and analyzed by gel-liquid chromatography-tandem MS and label-free quantitation. The proteomics analysis revealed novel changes in the ECM of AAA, including increased expression as well as degradation of collagen XII, thrombospondin 2, aortic carboxypeptidase-like protein, periostin, fibronectin and tenascin. Proteomics also confirmed the accumulation of macrophage metalloelastase (MMP-12). Incubation of control aortic tissue with recombinant MMP-12 resulted in the extensive fragmentation of these glycoproteins, most of which are novel substrates of MMP-12. In conclusion, our proteomics methodology allowed the first detailed analysis of the ECM in AAA and identified markers of pathological ECM remodeling related to MMP-12 activity.
authors: King's British Heart Foundation Centre, King's College London, London, UK.
authors: Athanasios
authors: A
authors: Didangelos
authors: Xiaoke
authors: X
authors: Yin
authors: Kaushik
authors: K
authors: Mandal
authors: Angelika
authors: A
authors: Saje
authors: Alberto
authors: A
authors: Smith
authors: Qingbo
authors: Q
authors: Xu
authors: Marjan
authors: M
authors: Jahangiri
authors: Manuel
authors: M
authors: Mayr
references: Protein Expr Purif. 2001 Mar;21(2):268-74
references: 11237688
references: Circulation. 1997 Oct 7;96(7):2115-7
references: 9337176
references: Circulation. 1997 Jan 7;95(1):205-12
references: 8994438
references: Mol Cell Biol. 2003 Aug;23(15):5401-8
references: 12861025
references: J Clin Invest. 2010 Feb;120(2):422-32
references: 20101093
references: J Vasc Surg. 1998 Oct;28(4):676-86
references: 9786264
references: Anal Chem. 2003 Sep 1;75(17):4646-58
references: 14632076
references: Arterioscler Thromb Vasc Biol. 2010 Jul;30(7):1325-32
references: 20431068
references: Anal Chem. 2005 Oct 1;77(19):6218-24
references: 16194081
references: Arterioscler Thromb Vasc Biol. 1996 Aug;16(8):963-70
references: 8696960
references: Surgery. 2005 Apr;137(4):457-62
references: 15800495
references: Arterioscler Thromb. 1994 Aug;14(8):1315-20
references: 8049193
references: Mol Cell Proteomics. 2006 Oct;5(10):1853-64
references: 16733263
references: Anal Biochem. 1968 Feb;22(2):195-210
references: 4171014
references: Cancer Res. 2002 Sep 15;62(18):5358-64
references: 12235007
references: Exp Cell Res. 1999 Mar 15;247(2):320-8
references: 10066359
references: Exp Cell Res. 2005 Sep 10;309(1):48-55
references: 15992798
references: Circulation. 2008 Dec 2;118(23):2382-92
references: 19047592
references: Anal Chem. 2002 Oct 15;74(20):5383-92
references: 12403597
references: Circulation. 1999 May 18;99(19):2503-9
references: 10330380
references: Atherosclerosis. 2001 Feb 1;154(2):367-76
references: 11166769
references: J Vasc Surg. 2008 Oct;48(4):808-14
references: 18639426
references: Nat Genet. 2006 May;38(5):500-1
references: 16642009
references: Mol Cell Proteomics. 2010 Jun;9(6):1296-313
references: 20190199
references: Mol Cell Proteomics. 2010 Mar;9(3):497-509
references: 20037178
references: Lab Invest. 1994 May;70(5):705-10
references: 8196366
references: Atherosclerosis. 2009 Jan;202(1):34-40
references: 18482727
references: J Vasc Surg. 1997 Oct;26(4):670-5
references: 9357470
references: J Clin Invest. 1998 Dec 1;102(11):1900-10
references: 9835614
references: J Thorac Cardiovasc Surg. 2008 Jul;136(1):65-72, 72.e1-3
references: 18603055
references: Angiology. 2010 Apr;61(3):238-42
references: 20053631
references: Atherosclerosis. 1975 Jul-Aug;22(1):1-17
references: 125595
references: Arterioscler Thromb Vasc Biol. 2010 Feb;30(2):269-75
references: 19910633
references: Arterioscler Thromb Vasc Biol. 2005 Oct;25(10):2135-42
references: 16123314
references: Mol Cell Proteomics. 2008 Aug;7(8):1452-9
references: 18448420
references: Mol Cell Proteomics. 2005 Oct;4(10):1487-502
references: 15979981
references: Circulation. 2009 Aug 4;120(5):427-36
references: 19620505
references: Am J Pathol. 2009 Mar;174(3):818-28
references: 19179605
references: J Biol Chem. 1998 Jun 19;273(25):15654-60
references: 9624159
references: Mol Cell Proteomics. 2010 Sep;9(9):2048-62
references: 20551380
references: J Clin Invest. 2004 Jul;114(2):300-8
references: 15254597
references: Ann Vasc Surg. 1999 Mar;13(2):236-7
references: 10072471
references: Anal Chem. 2004 Jul 15;76(14):4193-201
references: 15253663
references: J Clin Invest. 2000 Jun;105(11):1641-9
references: 10841523
references: Biochem J. 1973 Mar;131(3):535-40
references: 4269048
references: Circulation. 2009 Sep 15;120(11):983-91
references: 19720936
references: Nat Rev Cardiol. 2009 Jul;6(7):464-74
references: 19468292
references: Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8259-64
references: 12034879