{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:56:59Z","timestamp":1791277019841,"version":"4.1.0"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2015,4,22]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Experimental studies characterize adaptive immune response as a critical factor in the progression and complications of atherosclerosis. Yet, it is unclear whether these observations translate to the human situation. This study systematically evaluates cellular components of the adaptive immune response in a biobank of human aortas covering the full spectrum of atherosclerotic disease.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              A systematic analysis was performed on 114 well\u2010characterized perirenal aortic specimens with immunostaining for T\u2010cell subsets (CD3\/4\/8\/45RA\/45RO\/FoxP3) and the Th1\/non\u2010Th1\/Th17 ratio (CD4\n              <jats:sup>+<\/jats:sup>\n              T\u2010bet\n              <jats:sup>+<\/jats:sup>\n              \/CD4\n              <jats:sup>+<\/jats:sup>\n              T\u2010bet\n              <jats:sup>\u2212<\/jats:sup>\n              \/CD4\n              <jats:sup>+<\/jats:sup>\n              \/interleukin\u201017\n              <jats:sup>+<\/jats:sup>\n              double staining). CD20 and CD138 were used to identify B cells and plasma cells, while B\u2010cell maturation was evaluated by AID\/CD21 staining and expression of lymphoid homeostatic CXCL13. Scattered CD4 and CD8 cells with a T memory subtype were found in normal aorta and early, nonprogressive lesions. The total number of T cells increases in progressive atherosclerotic lesions (\u22481:5 CD4\/CD8 T\u2010cell ratio). A further increase in medial and adventitial T cells is found upon progression to vulnerable lesions.\n            <\/jats:p>\n            <jats:p xml:lang=\"en\">This critical stage is further hallmarked by de novo formation of adventitial lymphoidlike structures containing B cells and plasma cells, a process accompanied by transient expression of CXCL13. A dramatic reduction of T\u2010cell subsets, disappearance of lymphoid structures, and loss of CXCL13 expression characterize postruptured lesions. FoxP3 and Th17 T cells were minimally present throughout the atherosclerotic process.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Transient CXCL13 expression, restricted presence of B cells in human atherosclerosis, along with formation of nonfunctional extranodal lymphoid structures in the phase preceding plaque rupture, indicates a \u201ccritical\u201d change in the inflammatory footprint before and during plaque destabilization.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.114.001403","type":"journal-article","created":{"date-parts":[[2015,3,27]],"date-time":"2015-03-27T13:44:02Z","timestamp":1427463842000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":93,"title":["A Change in Inflammatory Footprint Precedes Plaque Instability: A Systematic Evaluation of Cellular Aspects of the Adaptive Immune Response in Human Atherosclerosis"],"prefix":"10.1161","volume":"4","author":[{"given":"R. A.","family":"van Dijk","sequence":"first","affiliation":[{"name":"Department of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. J. F.","family":"Duinisveld","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. F.","family":"Schaapherder","sequence":"additional","affiliation":[{"name":"Department of Transplantation Surgery, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Mulder\u2010Stapel","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. F.","family":"Hamming","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Kuiper","sequence":"additional","affiliation":[{"name":"Gorlaeus Laboratories, Division of Biopharmaceutics, Leiden Academic Centre for Drug Research, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O. J.","family":"de Boer","sequence":"additional","affiliation":[{"name":"Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. C.","family":"van der Wal","sequence":"additional","affiliation":[{"name":"Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. D.","family":"Kolodgie","sequence":"additional","affiliation":[{"name":"CVPath Institute Inc., Gaithersburg, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Virmani","sequence":"additional","affiliation":[{"name":"CVPath Institute Inc., Gaithersburg, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. H. N.","family":"Lindeman","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra043430"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1882"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R800092-JLR200"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.09.009"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1222878110"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2415"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.5.2731"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.070776"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.19.8.1960"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000779"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.carpath.2009.02.001"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2009.11.016"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.20.5.1262"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH12-06-0425"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901126"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/44309"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1230719"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2012.04.031"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10146"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn120"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.1619"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.10.006"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.21.2610"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2008.143461"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.06270611"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1159\/000076682"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1159\/000272940"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2004.019224"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2011.10.005"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9896(199906)188:2<174::AID-PATH333>3.0.CO;2-3"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.242180"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/1096-9896(2000)9999:9999<::AID-PATH774>3.0.CO;2-N"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2014.01.004"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2012.06.071"},{"key":"e_1_3_2_36_2","first-page":"S43","article-title":"The CXCL13\u2010CXCR5 axis contributes to atherosclerosis development in LDLr\u2212\/\u2212 mice by regulating lymphocyte migration to perivascular lymph organs","volume":"87","author":"Daissormont I","year":"2010","unstructured":"Daissormont I, Lipp M, Biessen EAL. The CXCL13\u2010CXCR5 axis contributes to atherosclerosis development in LDLr\u2212\/\u2212 mice by regulating lymphocyte migration to perivascular lymph organs. Cardiovasc Res. 2010;87:S43\u2013S44.","journal-title":"Cardiovasc Res"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2006.10.002"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100155"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7272"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(99)00011-8"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20070352"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.114.001403","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T10:52:27Z","timestamp":1715597547000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.114.001403"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,4,22]]},"references-count":40,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2015,4,22]]}},"alternative-id":["10.1161\/JAHA.114.001403"],"URL":"https:\/\/doi.org\/10.1161\/jaha.114.001403","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,4,22]]},"assertion":[{"value":"2014-11-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-01-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-02-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e001403"}}