{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:19:36Z","timestamp":1789017576670,"version":"build-2803163510"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2018,8]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis characterized by the infiltration of multiple tissues with lipid-laden histiocytes. Cardiovascular involvement is frequent in ECD and leads to a severe prognosis. The objective of this study was to determine whether an alteration of lipid metabolism participates in the lipid accumulation in histiocytes and the cardiovascular involvement in ECD.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              An analysis of plasma lipid levels indicated that male ECD patients carrying the\n              <jats:italic>BRAF<\/jats:italic>\n              <jats:sup>V600E<\/jats:sup>\n              (B-Raf proto-oncogene, serine\/threonine kinase) mutation exhibited hypoalphalipoproteinemia, as demonstrated by low plasma HDL-C (high-density lipoprotein cholesterol) levels. Capacity of sera from male\n              <jats:italic>BRAF<\/jats:italic>\n              <jats:sup>V600E<\/jats:sup>\n              ECD patients to mediate free cholesterol efflux from human macrophages was reduced compared with control individuals. Cardiovascular involvement was detected in 84% of the ECD patients, and we reported that the presence of the\n              <jats:italic>BRAF<\/jats:italic>\n              <jats:sup>V600E<\/jats:sup>\n              mutation and hypoalphalipoproteinemia is an independent determinant of aortic infiltration in ECD. Phenotyping of blood CD14\n              <jats:sup>+<\/jats:sup>\n              cells, the precursors of histiocytes, enabled the identification of a specific inflammatory signature associated with aortic infiltration which was partially affected by the HDL phenotype. Finally, the treatment with vemurafenib, an inhibitor of the\n              <jats:italic>BRAF<\/jats:italic>\n              <jats:sup>V600E<\/jats:sup>\n              mutation, restored the defective sera cholesterol efflux capacity and reduced the aortic infiltration.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              Our findings indicate that hypoalphalipoproteinemia in male ECD patients carrying the\n              <jats:italic>BRAF<\/jats:italic>\n              <jats:sup>V600E<\/jats:sup>\n              mutation favors the formation of lipid-laden histiocytes. In addition, we identified the\n              <jats:italic>BRAF<\/jats:italic>\n              status and the HDL phenotype as independent determinants of the aortic involvement in ECD with a potential role of HDL in modulating the infiltration of blood CD14\n              <jats:sup>+<\/jats:sup>\n              cells into the aorta.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.118.310803","type":"journal-article","created":{"date-parts":[[2018,6,21]],"date-time":"2018-06-21T09:00:54Z","timestamp":1529571654000},"page":"1913-1925","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Hypoalphalipoproteinemia and\n            <i>BRAF<\/i>\n            <sup>V600E<\/sup>\n            Mutation Are Major Predictors of Aortic Infiltration in the Erdheim-Chester Disease"],"prefix":"10.1161","volume":"38","author":[{"given":"Fleur","family":"Cohen-Aubart","sequence":"first","affiliation":[{"name":"From the Institut E3M, Centre National de R\u00e9f\u00e9rence des Maladies Rares Auto-Immunes et Syst\u00e9miques (F.C.-A., Z.A., J.H.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryse","family":"Guerin","sequence":"additional","affiliation":[{"name":"Inserm, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S1166, H\u00f4pital de la Piti\u00e9, Sorbonne Universit\u00e9, Paris, France (M.G., F.S.-C., Y.A., E.F., P.L., W.L.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"Poupel","sequence":"additional","affiliation":[{"name":"Inserm, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S1166, H\u00f4pital de la Piti\u00e9, Sorbonne Universit\u00e9, Paris, France (M.G., F.S.-C., Y.A., E.F., P.L., W.L.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Cluzel","sequence":"additional","affiliation":[{"name":"Cardiovascular and Interventional Radiology Department (P.C.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora","family":"Saint-Charles","sequence":"additional","affiliation":[{"name":"Inserm, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S1166, H\u00f4pital de la Piti\u00e9, Sorbonne Universit\u00e9, Paris, France (M.G., F.S.-C., Y.A., E.F., P.L., W.L.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Charlotte","sequence":"additional","affiliation":[{"name":"Department of Pathology (F.C.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youssef","family":"Arsafi","sequence":"additional","affiliation":[{"name":"Inserm, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S1166, H\u00f4pital de la Piti\u00e9, Sorbonne Universit\u00e9, Paris, France (M.G., F.S.-C., Y.A., E.F., P.L., W.L.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Emile","sequence":"additional","affiliation":[{"name":"EA4340, Versailles University, Paris-Saclay University, Boulogne, France (J.-F.E.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Frisdal","sequence":"additional","affiliation":[{"name":"Inserm, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S1166, H\u00f4pital de la Piti\u00e9, Sorbonne Universit\u00e9, Paris, France (M.G., F.S.-C., Y.A., E.F., P.L., W.L.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carine","family":"Le Goff","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Assistance Publique\u2013H\u00f4pitaux de Paris, H\u00f4pital Piti\u00e9-Salp\u00eatri\u00e8re, France; INSERM UMR1148, Laboratory of Vascular Translational Science, Bichat Hospital, Paris Diderot University, France (C.L.G.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Donadieu","sequence":"additional","affiliation":[{"name":"Haematology Department, Assistance Publique\u20136-H\u00f4pitaux de Paris, H\u00f4pital Trousseau, France (J.D.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahir","family":"Amoura","sequence":"additional","affiliation":[{"name":"From the Institut E3M, Centre National de R\u00e9f\u00e9rence des Maladies Rares Auto-Immunes et Syst\u00e9miques (F.C.-A., Z.A., J.H.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Lesnik","sequence":"additional","affiliation":[{"name":"Inovarion, Paris, France (L.P.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Haroche","sequence":"additional","affiliation":[{"name":"From the Institut E3M, Centre National de R\u00e9f\u00e9rence des Maladies Rares Auto-Immunes et Syst\u00e9miques (F.C.-A., Z.A., J.H.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfried","family":"Le Goff","sequence":"additional","affiliation":[{"name":"Inserm, Institute of Cardiometabolism and Nutrition (ICAN), UMR_S1166, H\u00f4pital de la Piti\u00e9, Sorbonne Universit\u00e9, Paris, France (M.G., F.S.-C., Y.A., E.F., P.L., W.L.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-690636"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.825075"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-12-757377"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-12-757823"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-05-430140"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-199605000-00005"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.142.2.7054817"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(96)90145-8"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2559.1997.d01-614.x"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870130335"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2013.02.028"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2012-202914"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.11264"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-10-313510"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22280"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-0495(97)90220-1"},{"key":"e_1_3_5_18_2","first-page":"297","article-title":"[Erdheim-Chester disease].","volume":"31","author":"Kujat C","year":"1991","unstructured":"Kujat, C, Martin, J, P\u00fcschel, W. 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