{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T14:31:59Z","timestamp":1769092319657,"version":"3.49.0"},"reference-count":41,"publisher":"Georg Thieme Verlag KG","issue":"06","funder":[{"name":"Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences","award":["2016-I2M-1\u2013009"],"award-info":[{"award-number":["2016-I2M-1\u2013009"]}]},{"name":"National Natural Science Funds","award":["81970308"],"award-info":[{"award-number":["81970308"]}]},{"name":"Fund of \u201cSanming\u201d Project of Medicine in Shenzhen","award":["SZSM201911017"],"award-info":[{"award-number":["SZSM201911017"]}]},{"name":"Shenzhen Key Medical Discipline Construction Fund","award":["SZXK001"],"award-info":[{"award-number":["SZXK001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:p>\n            Objective\u2003Aldehyde dehydrogenase 4A1 (ALDH4A1) was recently reported to be a novel autoantigen of atherosclerosis. However, its role in different phenotypes of acute coronary syndrome remains unclear. Herein, we planned to explore the circulating and regional expression of ALDH4A1 in patients with plaque rupture (PR) and plaque erosion (PE) determined by optical coherence tomography (OCT).<\/jats:p><jats:p>\n            Methods and Results\u2003After applying the inclusion and exclusion criteria, a prospective series of 312 patients with ST segment elevated myocardial infarction (STEMI), including 161 patients with PR and 151 patients with PE determined by OCT, were enrolled for plasma ALDH4A1 testing. In addition, ALDH4A1 was quantified using immunofluorescence in aspirated coronary thrombus samples obtained from 31 patients with PR and 25 patients with PE. In addition, we established an atherosclerosis mouse model and analyzed the distribution of ALDH4A1 expression in different mouse organs. Furthermore, we compared the level of ALDH4A1 in the spleen and carotid artery between Apoe\u2212\/\u2212 and C57 mice. The results showed that the plasma level of ALDH4A1 was significantly higher in STEMI patients with PE than in those with PR (4.6\u2009ng\/mL [2.2\u20138.7] vs. 3.5\u2009ng\/mL [1.6\u20135.6] p\u2009=\u20090.005). The expression of ALDH4A1 in aspirated coronary thrombi was also significantly higher in patients with PE than in those with PR (mean gray value: 32.0 [23.6\u201340.6] vs. 16.8 [14.0\u201324.5], p\u2009&lt;\u20090.001). In animal models, the expression of ALDH4A1 is much higher in the spleen than in other organs, and the level of ALDH4A1 is significantly elevated in the spleen and carotid artery of Apoe\u2212\/\u2212 mice compared with C57 mice.<\/jats:p><jats:p>\n            Conclusion\u2003The high levels of ALDH4A1 in the plasma and aspirated coronary thrombi independently correlated with PE in patients with STEMI. These results suggested that ALDH4A1 is involved in the mechanism of PE and serves as a promising biomarker and treatment target for patients with PE.<\/jats:p>","DOI":"10.1055\/s-0043-1777265","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T23:51:47Z","timestamp":1702943507000},"page":"584-594","source":"Crossref","is-referenced-by-count":4,"title":["Atherosclerotic Autoantigen ALDH4A1 as a Novel Immunological Indicator for Plaque Erosion in Patients with ST Segment Elevated Myocardial Infarction"],"prefix":"10.1055","volume":"124","author":[{"given":"Jiannan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China"},{"name":"Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1139-495X","authenticated-orcid":false,"given":"Runzhen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinying","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoxiao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China"},{"name":"Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China"},{"name":"Coronary Heart Disease Center, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2031-6438","authenticated-orcid":false,"given":"Hongbing","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, China"},{"name":"Coronary Heart Disease Center, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanjun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China"},{"name":"Coronary Heart Disease Center, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2023,12,18]]},"reference":[{"issue":"07","key":"ref1","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nrcardio.2014.62","article-title":"Clinical classification of plaque morphology in coronary disease","volume":"11","author":"F Otsuka","year":"2014","journal-title":"Nat Rev Cardiol"},{"issue":"10","key":"ref2","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1093\/eurheartj\/ehs411","article-title":"Update on acute coronary syndromes: the pathologists' view","volume":"34","author":"E Falk","year":"2013","journal-title":"Eur Heart J"},{"issue":"22","key":"ref3","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1093\/eurheartj\/ehx786","article-title":"Plaque erosion: a new in vivo diagnosis and a potential major shift in the management of patients with acute coronary syndromes","volume":"39","author":"R A Partida","year":"2018","journal-title":"Eur Heart J"},{"issue":"12","key":"ref4","doi-asserted-by":"crossref","first-page":"1472","DOI":"10.1016\/j.jcmg.2017.04.017","article-title":"Plaque rupture in coronary atherosclerosis is associated with increased plaque structural stress","volume":"10","author":"C Costopoulos","year":"2017","journal-title":"JACC Cardiovasc Imaging"},{"issue":"12","key":"ref5","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1161\/CIRCRESAHA.114.302721","article-title":"Mechanisms of plaque formation and rupture","volume":"114","author":"J F Bentzon","year":"2014","journal-title":"Circ Res"},{"issue":"01","key":"ref6","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1161\/CIRCRESAHA.117.310694","article-title":"Flow perturbation mediates neutrophil recruitment and potentiates endothelial injury via TLR2 in mice: implications for superficial erosion","volume":"121","author":"G Franck","year":"2017","journal-title":"Circ Res"},{"issue":"10","key":"ref7","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1161\/01.ATV.0000034021.92658.4C","article-title":"Differential accumulation of proteoglycans and hyaluronan in culprit lesions: insights into plaque erosion","volume":"22","author":"F D Kolodgie","year":"2002","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"13","key":"ref8","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1016\/j.jacc.2018.06.072","article-title":"Alterations of hyaluronan metabolism in acute coronary syndrome: implications for plaque erosion","volume":"72","author":"D Pedicino","year":"2018","journal-title":"J Am Coll Cardiol"},{"issue":"37","key":"ref9","doi-asserted-by":"crossref","first-page":"3561","DOI":"10.1093\/eurheartj\/ehaa721","article-title":"CD8 lymphocytes and plaque erosion: a new piece in the jigsaw","volume":"41","author":"G Liuzzo","year":"2020","journal-title":"Eur Heart J"},{"issue":"37","key":"ref10","doi-asserted-by":"crossref","first-page":"3549","DOI":"10.1093\/eurheartj\/ehaa703","article-title":"Differential immunological signature at the culprit site distinguishes acute coronary syndrome with intact from acute coronary syndrome with ruptured fibrous cap: results from the prospective translational OPTICO-ACS study","volume":"41","author":"D M Leistner","year":"2020","journal-title":"Eur Heart J"},{"issue":"12","key":"ref11","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1161\/CIRCULATIONAHA.117.029870","article-title":"Acute coronary syndromes: the way forward from mechanisms to precision treatment","volume":"136","author":"F Crea","year":"2017","journal-title":"Circulation"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"766","DOI":"10.1016\/j.ijcard.2015.11.030","article-title":"Plaque morphologies and the clinical prognosis of acute coronary syndrome caused by lesions with intact fibrous cap diagnosed by optical coherence tomography","volume":"203","author":"T Yonetsu","year":"2016","journal-title":"Int J Cardiol"},{"issue":"7841","key":"ref13","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/s41586-020-2993-2","article-title":"ALDH4A1 is an atherosclerosis auto-antigen targeted by protective antibodies","volume":"589","author":"C Lorenzo","year":"2021","journal-title":"Nature"},{"issue":"19","key":"ref14","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1016\/j.jacc.2013.05.071","article-title":"In vivo diagnosis of plaque erosion and calcified nodule in patients with acute coronary syndrome by intravascular optical coherence tomography","volume":"62","author":"H Jia","year":"2013","journal-title":"J Am Coll Cardiol"},{"issue":"03","key":"ref15","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1161\/CIRCRESAHA.113.301562","article-title":"A novel mouse model of atherosclerotic plaque instability for drug testing and mechanistic\/therapeutic discoveries using gene and microRNA expression profiling","volume":"113","author":"Y C Chen","year":"2013","journal-title":"Circ Res"},{"issue":"03","key":"ref16","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1002\/ar.22641","article-title":"Quantitative analysis of histological staining and fluorescence using ImageJ","volume":"296","author":"E C Jensen","year":"2013","journal-title":"Anat Rec (Hoboken)"},{"issue":"06","key":"ref17","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1177\/38.6.2110586","article-title":"Quantitative immunohistochemistry of synaptophysin in human neocortex: an alternative method to estimate density of presynaptic terminals in paraffin sections","volume":"38","author":"E Masliah","year":"1990","journal-title":"J Histochem Cytochem"},{"issue":"06","key":"ref18","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/nrneph.2017.51","article-title":"The immunology of atherosclerosis","volume":"13","author":"A Gister\u00e5","year":"2017","journal-title":"Nat Rev Nephrol"},{"issue":"01","key":"ref19","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.atherosclerosis.2008.05.025","article-title":"The autoimmune origin of atherosclerosis","volume":"201","author":"C Blasi","year":"2008","journal-title":"Atherosclerosis"},{"issue":"09","key":"ref20","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1093\/eurheartj\/ehaa995","article-title":"Alarmin-activated B cells accelerate murine atherosclerosis after myocardial infarction via plasma cell-immunoglobulin-dependent mechanisms","volume":"42","author":"T Kyaw","year":"2021","journal-title":"Eur Heart J"},{"issue":"10","key":"ref21","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1161\/CIRCRESAHA.121.320090","article-title":"Human coronary plaque T cells are clonal and cross-react to virus and self","volume":"130","author":"R R Chowdhury","year":"2022","journal-title":"Circ Res"},{"issue":"01","key":"ref22","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1161\/CIRCRESAHA.118.311098","article-title":"Reassessing the mechanisms of acute coronary syndromes","volume":"124","author":"P Libby","year":"2019","journal-title":"Circ Res"},{"issue":"21","key":"ref23","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1161\/01.CIR.100.21.2135","article-title":"Perturbation of the T-cell repertoire in patients with unstable angina","volume":"100","author":"G Liuzzo","year":"1999","journal-title":"Circulation"},{"issue":"22","key":"ref24","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1093\/eurheartj\/ehv044","article-title":"TLR2 and neutrophils potentiate endothelial stress, apoptosis and detachment: implications for superficial erosion","volume":"36","author":"T Quillard","year":"2015","journal-title":"Eur Heart J"},{"issue":"05","key":"ref25","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1097\/00041433-200410000-00012","article-title":"The accumulation of specific types of proteoglycans in eroded plaques: a role in coronary thrombosis in the absence of rupture","volume":"15","author":"F D Kolodgie","year":"2004","journal-title":"Curr Opin Lipidol"},{"issue":"10","key":"ref26","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1038\/s41591-019-0590-4","article-title":"Single-cell immune landscape of human atherosclerotic plaques","volume":"25","author":"D M Fernandez","year":"2019","journal-title":"Nat Med"},{"issue":"07","key":"ref27","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41569-020-0352-5","article-title":"T cell subsets and functions in atherosclerosis","volume":"17","author":"R Saigusa","year":"2020","journal-title":"Nat Rev Cardiol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.3389\/fimmu.2019.01084","article-title":"Macrophage polarization: different gene signatures in M1(LPS+) vs. classically and M2(LPS-) vs. alternatively activated macrophages","volume":"10","author":"M Orecchioni","year":"2019","journal-title":"Front Immunol"},{"issue":"23","key":"ref29","doi-asserted-by":"crossref","first-page":"10973","DOI":"10.1111\/jcmm.17018","article-title":"Difference of immune cell infiltration between stable and unstable carotid artery atherosclerosis","volume":"25","author":"J Gao","year":"2021","journal-title":"J Cell Mol Med"},{"issue":"04","key":"ref30","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1089\/ars.2017.7374","article-title":"Structural biology of proline catabolic enzymes","volume":"30","author":"J J Tanner","year":"2019","journal-title":"Antioxid Redox Signal"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.jprot.2017.02.009","article-title":"Downregulation of GNA13-ERK network in prefrontal cortex of schizophrenia brain identified by combined focused and targeted quantitative proteomics","volume":"158","author":"M Hirayama-Kurogi","year":"2017","journal-title":"J Proteomics"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"11","DOI":"10.7554\/eLife.74308","article-title":"Genetic variation in ALDH4A1 is associated with muscle health over the lifespan and across species","volume":"11","author":"O Villa","year":"2022","journal-title":"eLife"},{"issue":"10","key":"ref33","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1253\/circj.CJ-20-0942","article-title":"Impact of optical coherence tomography imaging on decision-making during percutaneous coronary intervention in patients presented with acute coronary syndromes","volume":"85","author":"A KM Khalifa","year":"2021","journal-title":"Circ J"},{"issue":"11","key":"ref34","first-page":"792","article-title":"Effective anti-thrombotic therapy without stenting: intravascular optical coherence tomography-based management in plaque erosion (the EROSION study)","volume":"38","author":"H Jia","year":"2017","journal-title":"Eur Heart J"},{"issue":"06","key":"ref35","doi-asserted-by":"crossref","first-page":"497","DOI":"10.4244\/EIJ-D-20-00299","article-title":"Predictors of non-stenting strategy for acute coronary syndrome caused by plaque erosion: four-year outcomes of the EROSION study","volume":"17","author":"L He","year":"2021","journal-title":"EuroIntervention"},{"issue":"12","key":"ref36","doi-asserted-by":"crossref","first-page":"e005860","DOI":"10.1161\/CIRCINTERVENTIONS.117.005860","article-title":"EROSION study (Effective Anti-Thrombotic Therapy Without Stenting: Intravascular Optical Coherence Tomography-Based Management in Plaque Erosion): a 1-year follow-up report","volume":"10","author":"L Xing","year":"2017","journal-title":"Circ Cardiovasc Interv"},{"issue":"12","key":"ref37","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1161\/01.CIR.0000159354.43778.69","article-title":"In vivo characterization of coronary atherosclerotic plaque by use of optical coherence tomography","volume":"111","author":"I K Jang","year":"2005","journal-title":"Circulation"},{"issue":"19","key":"ref38","doi-asserted-by":"crossref","first-page":"1838","DOI":"10.1056\/NEJMoa2021372","article-title":"Colchicine in patients with chronic coronary disease","volume":"383","author":"S M Nidorf","year":"2020","journal-title":"N Engl J Med"},{"issue":"12","key":"ref39","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1056\/NEJMoa1707914","article-title":"Antiinflammatory therapy with canakinumab for atherosclerotic disease","volume":"377","author":"P M Ridker","year":"2017","journal-title":"N Engl J Med"},{"issue":"24","key":"ref40","doi-asserted-by":"crossref","first-page":"2299","DOI":"10.1161\/CIRCULATIONAHA.120.049981","article-title":"Association between immune checkpoint inhibitors with cardiovascular events and atherosclerotic plaque","volume":"142","author":"Z D Drobni","year":"2020","journal-title":"Circulation"},{"issue":"09","key":"ref41","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1161\/CIRCRESAHA.120.315942","article-title":"Vaccination strategies and immune modulation of atherosclerosis","volume":"126","author":"J Nilsson","year":"2020","journal-title":"Circ Res"}],"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0043-1777265.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T16:59:23Z","timestamp":1730825963000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0043-1777265"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,18]]},"references-count":41,"journal-issue":{"issue":"06","published-online":{"date-parts":[[2024,5,24]]},"published-print":{"date-parts":[[2024,6]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0043-1777265","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"value":"0340-6245","type":"print"},{"value":"2567-689X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,18]]}}}