{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T05:30:09Z","timestamp":1791178209894,"version":"4.1.0"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Circ Cardiovasc Genet"],"published-print":{"date-parts":[[2013,2]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Matrix metalloproteinases (MMPs) play a key role in cardiovascular disease, in particular aneurysm formation and plaque rupture. Surprisingly, little is known about MMP substrates in the vasculature.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>We used a proteomics approach to identify vascular substrates for 3 MMPs, 1 of each of the 3 major classes of MMPs: Human arteries were incubated with MMP-3 (a member of stromelysins), MMP-9 (considered a gelatinase), and MMP-14 (considered a member of the collagenases and of the membrane-bound MMPs). Candidate substrates were identified by mass spectrometry based on increased release from the arterial tissue on digestion, spectral evidence for proteolytic degradation after gel separation, and identification of nontryptic cleavage sites. Using this approach, novel candidates were identified, including extracellular matrix proteins associated with the basement membrane, elastic fibers (emilin-1), and other extracellular proteins (periostin, tenascin-X). Seventy-four nontryptic cleavage sites were detected, many of which were shared among different MMPs. The proteomics findings were validated by immunoblotting and by digesting recombinant\/purified proteins with exogenous MMPs. As proof-of-principle, results were related to in vivo pathology by searching for corresponding degradation products in human aortic tissue with different levels of endogenous MMP-9.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>The application of proteomics to identify MMP targets is a new frontier in cardiovascular research. Our current classification of MMPs based on few substrates is an oversimplification of a complex area of biology. This study provides a more comprehensive assessment of potential MMP substrates in the vasculature and represents a valuable resource for future investigations.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgenetics.112.964452","type":"journal-article","created":{"date-parts":[[2012,12,20]],"date-time":"2012-12-20T11:19:19Z","timestamp":1356002359000},"page":"106-117","source":"Crossref","is-referenced-by-count":54,"title":["Proteomic Identification of Matrix Metalloproteinase Substrates in the Human Vasculature"],"prefix":"10.1161","volume":"6","author":[{"given":"Christin","family":"Stegemann","sequence":"first","affiliation":[{"name":"From the King\u2019s British Heart Foundation Centre, King\u2019s College London, London, United Kingdom (C.S., A.D., J.B.-B., S.L., M.M.); The James Black Centre, King\u2019s College London, London, United Kingdom (C.S., A.D., J.B.-B., S.L., M.M.); Division of Cardiac Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD (K.M.); and Department of Cardiac Surgery, St. George\u2019s Healthcare NHS Trust, London, United Kingdom (M.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athanasios","family":"Didangelos","sequence":"additional","affiliation":[{"name":"From the King\u2019s British Heart Foundation Centre, King\u2019s College London, London, United Kingdom (C.S., A.D., J.B.-B., S.L., M.M.); The James Black Centre, King\u2019s College London, London, United Kingdom (C.S., A.D., J.B.-B., S.L., M.M.); Division of Cardiac Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD (K.M.); and Department of Cardiac Surgery, St. George\u2019s Healthcare NHS Trust, London, United Kingdom (M.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Barallobre-Barreiro","sequence":"additional","affiliation":[{"name":"From the King\u2019s British Heart Foundation Centre, King\u2019s College London, London, United Kingdom (C.S., A.D., J.B.-B., S.L., M.M.); The James Black Centre, King\u2019s College London, London, United Kingdom (C.S., A.D., J.B.-B., S.L., M.M.); Division of Cardiac Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD (K.M.); and Department of Cardiac Surgery, St. George\u2019s Healthcare NHS Trust, London, United Kingdom (M.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah R.","family":"Langley","sequence":"additional","affiliation":[{"name":"From the King\u2019s British Heart Foundation Centre, King\u2019s College London, London, United Kingdom (C.S., A.D., J.B.-B., S.L., M.M.); The James Black Centre, King\u2019s College London, London, United Kingdom (C.S., A.D., J.B.-B., S.L., M.M.); Division of Cardiac Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD (K.M.); and Department of Cardiac Surgery, St. George\u2019s Healthcare NHS Trust, London, United Kingdom (M.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaushik","family":"Mandal","sequence":"additional","affiliation":[{"name":"From the King\u2019s British Heart Foundation Centre, King\u2019s College London, London, United Kingdom (C.S., A.D., J.B.-B., S.L., M.M.); The James Black Centre, King\u2019s College London, London, United Kingdom (C.S., A.D., J.B.-B., S.L., M.M.); Division of Cardiac Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD (K.M.); and Department of Cardiac Surgery, St. George\u2019s Healthcare NHS Trust, London, United Kingdom (M.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjan","family":"Jahangiri","sequence":"additional","affiliation":[{"name":"From the King\u2019s British Heart Foundation Centre, King\u2019s College London, London, United Kingdom (C.S., A.D., J.B.-B., S.L., M.M.); The James Black Centre, King\u2019s College London, London, United Kingdom (C.S., A.D., J.B.-B., S.L., M.M.); Division of Cardiac Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD (K.M.); and Department of Cardiac Surgery, St. George\u2019s Healthcare NHS Trust, London, United Kingdom (M.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Mayr","sequence":"additional","affiliation":[{"name":"From the King\u2019s British Heart Foundation Centre, King\u2019s College London, London, United Kingdom (C.S., A.D., J.B.-B., S.L., M.M.); The James Black Centre, King\u2019s College London, London, United Kingdom (C.S., A.D., J.B.-B., S.L., M.M.); Division of Cardiac Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD (K.M.); and Department of Cardiac Surgery, St. George\u2019s Healthcare NHS Trust, London, United Kingdom (M.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2012.01.007"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.31.21491"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000150046.48115.80"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2005.08.002"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000196986.50059.e0"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M900275-MCP200"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.111.056952"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M800203-MCP200"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1997.00751.x"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj2030209"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.17.10079"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003226-199609000-00009"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M000050-MCP201"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01775-07"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00036a018"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(94)00960-0"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.15.8650"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.23654"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M000032-MCP201"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)02249-3"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M110.001693"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M111.008128"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.110.957811"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2011.09.043"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm858"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0305862101"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M800449-MCP200"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.10.7312"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1408"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2010.178"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.06.038"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt810"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1611"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C112.350785"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.110.959098"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.115.14.2817"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.109.872663"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng850"},{"key":"e_1_3_4_40_2","first-page":"8586","article-title":"Interference of tenascin-C with syndecan-4 binding to fibronectin blocks cell adhesion and stimulates tumor cell proliferation.","volume":"61","author":"Huang W","year":"2001","unstructured":"Huang W, Chiquet-Ehrismann R, Moyano JV, Garcia-Pardo A, Orend G. 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