{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:17:45Z","timestamp":1792685865554,"version":"4.5.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2014,3,14]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Neutrophil extracellular trap (NET) formation promotes vascular damage, thrombosis, and activation of interferon-\u03b1\u2013producing plasmacytoid dendritic cells in diseased arteries. Peptidylarginine deiminase inhibition is a strategy that can decrease in vivo NET formation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>To test whether peptidylarginine deiminase inhibition, a novel approach to targeting arterial disease, can reduce vascular damage and inhibit innate immune responses in murine models of atherosclerosis.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              <jats:italic>Apolipoprotein-E (Apoe<\/jats:italic>\n              )\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice demonstrated enhanced NET formation, developed autoantibodies to NETs, and expressed high levels of interferon-\u03b1 in diseased arteries.\n              <jats:italic>Apoe<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice were treated for 11 weeks with daily injections of Cl-amidine, a peptidylarginine deiminase inhibitor. Peptidylarginine deiminase inhibition blocked NET formation, reduced atherosclerotic lesion area, and delayed time to carotid artery thrombosis in a photochemical injury model. Decreases in atherosclerosis burden were accompanied by reduced recruitment of netting neutrophils and macrophages to arteries, as well as by reduced arterial interferon-\u03b1 expression.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Pharmacological interventions that block NET formation can reduce atherosclerosis burden and arterial thrombosis in murine systems. These results support a role for aberrant NET formation in the pathogenesis of atherosclerosis through modulation of innate immune responses.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.114.303312","type":"journal-article","created":{"date-parts":[[2014,1,15]],"date-time":"2014-01-15T06:43:40Z","timestamp":1389768220000},"page":"947-956","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":445,"title":["Peptidylarginine Deiminase Inhibition Reduces Vascular Damage and Modulates Innate Immune Responses in Murine Models of Atherosclerosis"],"prefix":"10.1161","volume":"114","author":[{"given":"Jason S.","family":"Knight","sequence":"first","affiliation":[{"name":"From the Department of Rheumatology (J.S.K., A.A.O., S.Y., R.C.G.) and Cardiology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI (W.L., C.G., D.T.E.); Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD (W.Z., M.J.K.); and Department of Chemistry, The Scripps Research Institute, Jupiter, FL (V.S., P.R.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Luo","sequence":"additional","affiliation":[{"name":"From the Department of Rheumatology (J.S.K., A.A.O., S.Y., R.C.G.) and Cardiology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI (W.L., C.G., D.T.E.); Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD (W.Z., M.J.K.); and Department of Chemistry, The Scripps Research Institute, Jupiter, FL (V.S., P.R.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander A.","family":"O\u2019Dell","sequence":"additional","affiliation":[{"name":"From the Department of Rheumatology (J.S.K., A.A.O., S.Y., R.C.G.) and Cardiology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI (W.L., C.G., D.T.E.); Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD (W.Z., M.J.K.); and Department of Chemistry, The Scripps Research Institute, Jupiter, FL (V.S., P.R.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srilakshmi","family":"Yalavarthi","sequence":"additional","affiliation":[{"name":"From the Department of Rheumatology (J.S.K., A.A.O., S.Y., R.C.G.) and Cardiology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI (W.L., C.G., D.T.E.); Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD (W.Z., M.J.K.); and Department of Chemistry, The Scripps Research Institute, Jupiter, FL (V.S., P.R.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenpu","family":"Zhao","sequence":"additional","affiliation":[{"name":"From the Department of Rheumatology (J.S.K., A.A.O., S.Y., R.C.G.) and Cardiology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI (W.L., C.G., D.T.E.); Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD (W.Z., M.J.K.); and Department of Chemistry, The Scripps Research Institute, Jupiter, FL (V.S., P.R.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkataraman","family":"Subramanian","sequence":"additional","affiliation":[{"name":"From the Department of Rheumatology (J.S.K., A.A.O., S.Y., R.C.G.) and Cardiology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI (W.L., C.G., D.T.E.); Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD (W.Z., M.J.K.); and Department of Chemistry, The Scripps Research Institute, Jupiter, FL (V.S., P.R.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiao","family":"Guo","sequence":"additional","affiliation":[{"name":"From the Department of Rheumatology (J.S.K., A.A.O., S.Y., R.C.G.) and Cardiology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI (W.L., C.G., D.T.E.); Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD (W.Z., M.J.K.); and Department of Chemistry, The Scripps Research Institute, Jupiter, FL (V.S., P.R.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Grenn","sequence":"additional","affiliation":[{"name":"From the Department of Rheumatology (J.S.K., A.A.O., S.Y., R.C.G.) and Cardiology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI (W.L., C.G., D.T.E.); Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD (W.Z., M.J.K.); and Department of Chemistry, The Scripps Research Institute, Jupiter, FL (V.S., P.R.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R.","family":"Thompson","sequence":"additional","affiliation":[{"name":"From the Department of Rheumatology (J.S.K., A.A.O., S.Y., R.C.G.) and Cardiology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI (W.L., C.G., D.T.E.); Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD (W.Z., M.J.K.); and Department of Chemistry, The Scripps Research Institute, Jupiter, FL (V.S., P.R.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel T.","family":"Eitzman","sequence":"additional","affiliation":[{"name":"From the Department of Rheumatology (J.S.K., A.A.O., S.Y., R.C.G.) and Cardiology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI (W.L., C.G., D.T.E.); Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD (W.Z., M.J.K.); and Department of Chemistry, The Scripps Research Institute, Jupiter, FL (V.S., P.R.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana J.","family":"Kaplan","sequence":"additional","affiliation":[{"name":"From the Department of Rheumatology (J.S.K., A.A.O., S.Y., R.C.G.) and Cardiology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI (W.L., C.G., D.T.E.); Systemic Autoimmunity Branch, Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD (W.Z., M.J.K.); and Department of Chemistry, The Scripps Research Institute, Jupiter, FL (V.S., P.R.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.111.257535"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.107.154807"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.090480"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.961714"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.046755"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.112.265868"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092385"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201203170"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032366"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2010.06.006"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3001201"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3001180"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100450"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2010.06.008"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.30165"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.112.251314"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.107.697789"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.34504"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.111.242859"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1005743107"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04544.x"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20112322"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00360"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2012.00307"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm2008985"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI67390"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1001620"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi061180d"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2008.05.021"},{"key":"e_1_3_5_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2011.10.012"},{"key":"e_1_3_5_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.107.717595"},{"key":"e_1_3_5_33_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0703340"},{"key":"e_1_3_5_34_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-08-3323"},{"key":"e_1_3_5_35_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.193.7.863"},{"key":"e_1_3_5_36_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902199"},{"key":"e_1_3_5_37_2","doi-asserted-by":"publisher","DOI":"10.1177\/0961203309353773"},{"key":"e_1_3_5_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.06.044"},{"key":"e_1_3_5_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.9.11.5062"},{"key":"e_1_3_5_40_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.113.301627"},{"key":"e_1_3_5_41_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH11-09-0650"},{"key":"e_1_3_5_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.37961"},{"key":"e_1_3_5_43_2","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e3283562c3e"},{"key":"e_1_3_5_44_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1301059110"},{"key":"e_1_3_5_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2011.05.020"},{"key":"e_1_3_5_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2012.12.004"},{"key":"e_1_3_5_47_2","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e328363eba3"},{"key":"e_1_3_5_48_2","first-page":"612","article-title":"Atherosclerosis and cardiovascular disease in the spondyloarthritides, particularly ankylosing spondylitis and psoriatic arthritis.","volume":"31","author":"Papagoras C","year":"2013","unstructured":"Papagoras C, Voulgari PV, Drosos AA. Atherosclerosis and cardiovascular disease in the spondyloarthritides, particularly ankylosing spondylitis and psoriatic arthritis. Clin Exp Rheumatol. 2013;31:612\u2013620.","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_3_5_49_2","doi-asserted-by":"publisher","DOI":"10.1097\/RHU.0b013e31827846b1"}],"container-title":["Circulation Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCRESAHA.114.303312","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T03:20:39Z","timestamp":1715570439000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCRESAHA.114.303312"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3,14]]},"references-count":48,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2014,3,14]]}},"alternative-id":["10.1161\/CIRCRESAHA.114.303312"],"URL":"https:\/\/doi.org\/10.1161\/circresaha.114.303312","relation":{},"ISSN":["0009-7330","1524-4571"],"issn-type":[{"value":"0009-7330","type":"print"},{"value":"1524-4571","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3,14]]},"assertion":[{"value":"2013-12-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-01-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-01-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}