Proteomic analysis of calcified abdominal and thoracic aortic aneurysms

Matsumoto,Ken-Ichi; Maniwa,Tomoko; Tanaka,Tetsuya; Satoh,Kazumi; Okunishi,Hideki; Oda,Teiji

doi:10.3892/ijmm.2012.985

Proteomic analysis of calcified abdominal and thoracic aortic aneurysms

Authors:
- Ken-Ichi Matsumoto
- Tomoko Maniwa
- Tetsuya Tanaka
- Kazumi Satoh
- Hideki Okunishi
- Teiji Oda
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Affiliations: Department of Biosignaling and Radioisotope Experiment, Center for Integrated Research in Science, Shimane University, Izumo, Japan, Department of Pharmacology, Shimane University School of Medicine, Izumo, Japan, Division of Cardiovascular and Thoracic Surgery, Department of Surgery, Shimane University School of Medicine, Izumo, Japan
Published online on: April 30, 2012 https://doi.org/10.3892/ijmm.2012.985
Pages: 417-429

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Abstract

Aortic aneurysm is a complex multifactorial disease with genetic and environmental risk factors. It is often accompanied by aortic calcification. Here, to uncover proteins that are significantly changed in calcified abdominal aortic aneurysms (CAAs) and calcified thoracic aortic aneurysms (CTAs) compared with those in adjacent normal aorta tissues, comprehensive analysis of differentially expressed proteins in their tissues was performed by a quantitative proteomic approach with iTRAQ labeling in combination with nanoLC-MALDI-TOF/TOF-MS/MS followed by ProteinPilot analysis. The proteomic analysis revealed 138 and 134 proteins differentially expressed in CAAs and CTAs in contrast to neighboring normal aorta tissues with high confidence, respectively. Significantly increased expression (≥1.3-fold) was found in 41 and 28 proteins, whereas decreased expression (<0.77-fold) was found in 4 and 60 proteins in CAAs and CTAs, respectively. Among them, we identified already known proteins involved in aneurysm formation and vascular calcification, such as type I and III collagen, matrix Gla protein, and α-2-HS-glycoprotein in CAAs and fibrinogen α, β and γ chains and α-2-HS-glycoprotein in CTAs with increased expression and mimecan in CAAs and fibulin-5 in CTAs with decreased expression. Based on the Panther pathway and Genesis clustering analyses, some of the proteins could be linked to corresponding biochemical pathways, such as the integrin signaling pathway with increased expression in CAAs, the blood coagulation pathway with increased expression in CTAs, and the inflammation mediated by chemokine and cytokine signaling pathway and the glycolysis pathway with decreased expression in CTAs. Interestingly, it was found by clustering analysis that samples from CAAs of patients with both CAAs and CTAs were clustered outside the samples of patients with CAAs and were clustered with samples of patients with CTAs. Our results provide a comprehensive patient-based proteomic analysis for the identification of potential biomarkers for CAAs and CTAs.

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1.	S AnnambhotlaS BourgeoisX WangPH LinQ YaoC ChenRecent advances in molecular mechanisms of abdominal aortic aneurysm formationWorld J Surg32976986200810.1007/s00268-007-9456-x18259804
2.	ZS GalisJJ KhatriMatrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the uglyCirc Res90251262200211861412
3.	H KuivaniemiCD PlatsoucasMD Tilson IIIAortic aneurysms: an immune disease with a strong genetic componentCirculation117242252200810.1161/CIRCULATIONAHA.107.69098218195185
4.	H Abdul-HussienRG SoekhoeE WeberCollagen degradation in the abdominal aneurysm: a conspiracy of matrix metalloproteinase and cysteine collagenasesAm J Pathol170809817200710.2353/ajpath.2007.06052217322367
5.	EL HendersonYJ GengGK SukhovaAD WhittemoreJ KnoxP LibbyDeath of smooth muscle cells and expression of mediators of apoptosis by T lymphocytes in human abdominal aortic aneurysmsCirculation9996104199910.1161/01.CIR.99.1.969884385
6.	J GolledgeJ MullerA DaughertyP NormanAbdominal aortic aneurysm: pathogenesis and implications for managementArterioscler Thromb Vasc Biol2626052613200610.1161/01.ATV.0000245819.32762.cb16973970
7.	D ReedC ReedG StemmermannT HayashiAre aortic aneurysms caused by atherosclerosis?Circulation85205211199210.1161/01.CIR.85.1.2051728451
8.	JM RuddyJA JonesFG SpinaleJS IkonomidisRegional heterogeneity within the aorta: relevance to aneurysm diseaseJ Thorac Cardiovasc Surg13611231130200810.1016/j.jtcvs.2008.06.02719026791
9.	V LesauskaiteP TanganelliC SassiSmooth muscle cells of the media in the dilatative pathology of ascending thoracic aorta: morphology, immunoreactivity for osteopontin, matrix metalloproteinases, and their inhibitorsHum Pathol3210031011200110.1053/hupa.2001.27107
10.	MA CoadyJA RizzoLJ GoldsteinJA ElefteriadesNatural history, pathogenesis, and etiology of thoracic aortic aneurysms and dissectionsCardiol Clin17615635199910.1016/S0733-8651(05)70105-310589336
11.	JA RumbergerDB SimonsLA FitzpatrickPF SheedyRS SchwartzCoronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area. A histopathologic correlative studyCirculation9221572162199510.1161/01.CIR.92.8.2157
12.	CM ShanahanMechanisms of vascular calcification in renal diseaseClin Nephrol63146157200510.5414/CNP6314615730057
13.	S LehtoL NiskanenM SuhonenT RönnemaaM LaaksoMedial artery calcification. A neglected harbinger of cardiovascular complications in non-insulin-dependent diabetes mellitusArterioscler Thromb Vasc Biol16978983199610.1161/01.ATV.16.8.978
14.	G RusanescuR WeisslederE AikawaNotch signaling in cardiovascular disease and calcificationCurr Cardiol Rev4148156200810.2174/15734030878516055219936191
15.	J KendrickM ChoncholThe role of phosphorus in the development and progression of vascular calcificationAm J Kidney Dis58826834201110.1053/j.ajkd.2011.07.02021956015
16.	A DidangelosX YinK MandalExtracellular matrix composition and remodeling in human abdominal aortic aneurysms: a proteomics approachMol Cell Proteomics10M111.008128201110.1074/mcp.M111.00812821593211
17.	WS TungJK LeeRW ThompsonSimultaneous analysis of 1176 gene products in normal human aorta and abdominal aortic aneurysms using a membrane-based complementary DNA expression arrayJ Vasc Surg34143150200110.1067/mva.2001.113310
18.	TS AbsiTM Sundt IIIWS TungAltered patterns of gene expression distinguishing ascending aortic aneurysms from abdominal aortic aneurysms: complementary DNA expression profiling in the molecular characterization of aortic diseaseJ Thorac Cardiovasc Surg126344357200310.1016/S0022-5223(02)73576-9
19.	PL RossYN HuangJN MarcheseMultiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagentsMol Cell Proteomics3115411692004
20.	K MatsumotoPhosphorylation of extracellular matrix tenascin-X detected by differential mass tagging followed by nanoLC-MALDI-TOF/TOF-MS/MS using ProteinPilot softwareConnect Tissue Res53106116201210.3109/03008207.2011.611600
21.	IV ShilovSL SeymourAA PatelThe Paragon Algorithm, a next generation search engine that uses sequence temperature values and feature probabilities to identify peptides from tandem mass spectraMol Cell Proteomics616381655200710.1074/mcp.T600050-MCP200
22.	A SturnJ QuackenbushZ TrajanoskiGenesis: cluster analysis of microarray dataBioinformatics18207208200210.1093/bioinformatics/18.1.20711836235
23.	X WangSA LeMaireL ChenIncreased collagen deposition and elevated expression of connective tissue growth factor in human thoracic aortic dissectionCirculation114Suppl 1I200I205200610.1161/CIRCULATIONAHA.105.000240
24.	Z TouatL LepageV OllivierDilation-dependent activation of platelets and prothrombin in human thoracic ascending aortic aneurysmArterioscler Thromb Vasc Biol28940946200810.1161/ATVBAHA.107.158576
25.	X WangSA LeMaireL ChenDecreased expression of fibulin-5 correlates with reduced elastin in thoracic aortic dissectionSurgery138352359200510.1016/j.surg.2005.06.00616153447
26.	R WallinN WajihGT GreenwoodDC SaneArterial calcification: a review of mechanisms, animal models, and the prospects for therapyMed Res Rev21274301200110.1002/med.101011410932
27.	LT JensenNB HøstCollagen: scaffold for repair or executionCardiovasc Res33535539199710.1016/S0008-6363(96)00247-79093523
28.	T NakamuraPR LozanoY IkedaFibulin-5/DANCE is essential for elastogenesis in vivoNature415171175200210.1038/415171a11805835
29.	R RezgFC BarretoDV BarretoS LiabeufTB DrüekeZA MassyInhibitors of vascular calcification as potential therapeutic targetsJ Nephrol24416427201110.5301/JN.2011.842021688249
30.	HM SpronkBA SouteLJ SchurgersMatrix Gla protein accumulates at the border of regions of calcification and normal tissue in the media of the arterial vessel wallBiochem Biophys Res Commun289485490200110.1006/bbrc.2001.599611716499
31.	RM KraussYA KesäniemiCardiovascular disease and hyperlipidaemiaCurr Opin Lipidol5249251199410.1097/00041433-199408000-000017981954
32.	J GolledgeF van BockxmeerK JamrozikM McCannPE NormanAssociation between serum lipoproteins and abdominal aortic aneurysmAm J Cardiol105249251201010.1016/j.amjcard.2009.12.076
33.	K GreenowNJ PearceDP RamjiThe key role of apolipoprotein E in atherosclerosisJ Mol Med83329342200510.1007/s00109-004-0631-315827760
34.	G WalldiusI JungnerThe apoB/apoA-I ratio: a strong, new risk factor for cardiovascular disease and a target for lipid-lowering therapy-a review of the evidenceJ Intern Med259493519200610.1111/j.1365-2796.2006.01643.x16629855
35.	A TailleuxP DuriezJC FruchartV ClaveyApolipoprotein A-II, HDL metabolism and atherosclerosisAtherosclerosis164113200210.1016/S0021-9150(01)00751-112119188
36.	S StanE DelvinM LambertE SeidmanE LevyApo A-IV: an update on regulation and physiologic functionsBiochim Biophys Acta1631177187200310.1016/S1388-1981(03)00004-012633684
37.	A KawakamiM YoshidaApolipoprotein CIII links dyslipidemia with atherosclerosisJ Atheroscler Thromb16611200910.5551/jat.E60719262004
38.	M SadekRL HynecekS GoldenbergKC KentML MarinPL FariesGene expression analysis of a porcine native abdominal aortic aneurysm modelSurgery144252258200810.1016/j.surg.2008.04.00718656633
39.	JB MichelJL Martin-VenturaJ EgidoNovel aspects of the pathogenesis of aneurysms of the abdominal aorta in humansCardiovasc Res901827201110.1093/cvr/cvq33721037321
40.	JJ StecH SilbershatzGH ToflerAssociation of fibrinogen with cardiovascular risk factors and cardiovascular disease in the Framingham Offspring PopulationCirculation10216341638200010.1161/01.CIR.102.14.163411015340
41.	ML McCormickD GavrilaNL WeintraubRole of oxidative stress in the pathogenesis of abdominal aortic aneurysmsArterioscler Thromb Vasc Biol27461469200710.1161/01.ATV.0000257552.94483.1417218601
42.	K GroteI FlachM LuchtefeldMechanical stretch enhances mRNA expression and proenzyme release of matrix metalloproteinase-2 (MMP-2) via NAD(P)H oxidase-derived reactive oxygen speciesCirc Res92e80e86200310.1161/01.RES.0000077044.60138.7C
43.	MA DubickGC HunterS CaseyCL KeenAortic ascorbic acid, trace elements, and superoxide dismutase activity in human aneurysmal and occlusive diseaseProc Soc Exp Biol Med184138143198710.3181/00379727-184-424573809168
44.	JW StephensBC BainSE HumphriesGene-environment interaction and oxidative stress in cardiovascular diseaseAtherosclerosis200229238200810.1016/j.atherosclerosis.2008.04.00318490019
45.	S SukhanovY HigashiSY ShaiNovel effect of oxidized low-density lipoprotein: cellular ATP depletion via downregulation of glyceraldehyde-3-phosphate dehydrogenaseCirc Res99191200200610.1161/01.RES.0000232319.02303.8c