{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T21:18:33Z","timestamp":1770844713856,"version":"3.50.1"},"reference-count":47,"publisher":"American Society of Hematology","issue":"19","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,5,13]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypercholesterolemia is associated with elevated peripheral blood leukocytes and increased platelet levels, generally attributed to cholesterol-induced proinflammatory cytokines. Bone marrow (BM) cell mobilization and platelet production is achieved by disrupting the SDF-1:CXCR4 axis, namely with granulocyte colony-stimulating factor and\/or CXCR4 antagonists. Here we show that high cholesterol disrupts the BM SDF-1:CXCR4 axis; promotes the mobilization of B cells, neutrophils, and progenitor cells (HPCs); and creates thrombocytosis. Hypercholesterolemia was achieved after a 30-day high-cholesterol feeding trial, resulting in elevated low-density lipoprotein (LDL) cholesterol levels and inversion of the LDL to high-density lipoprotein cholesterol ratio. Hypercholesterolemic mice displayed lymphocytosis, increased neutrophils, HPCs, and thrombocytosis with a lineage-specific decrease in the BM. Histologic analysis revealed that megakaryocyte numbers remained unaltered but, in high-cholesterol mice, they formed large clusters in contact with BM vessels. In vitro, LDL induced stromal cell\u2013derived factor-1 (SDF-1) production, suggesting that megakaryocyte delocalization resulted from an altered SDF-1 gradient. LDL also stimulated B cells and HPC migration toward SDF-1, which was blocked by scavenger receptor class B type I (cholesterol receptor) inhibition. Accordingly, hypercholesterolemic mice had increased peripheral blood SDF-1 levels, increased platelets, CXCR4-positive B lymphocytes, neutrophils, and HPCs. High cholesterol interferes with the BM SDF-1:CXCR4 axis, resulting in lymphocytosis, thrombocytosis, and HPC mobilization.<\/jats:p>","DOI":"10.1182\/blood-2009-08-240580","type":"journal-article","created":{"date-parts":[[2009,12,16]],"date-time":"2009-12-16T04:33:40Z","timestamp":1260938020000},"page":"3886-3894","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":109,"title":["Hypercholesterolemia promotes bone marrow cell mobilization by perturbing the SDF-1:CXCR4 axis"],"prefix":"10.1182","volume":"115","author":[{"given":"Ana L.","family":"Gomes","sequence":"first","affiliation":[{"name":"Angiogenesis Group, Instituto Portugu\u00eas de Oncologia de Francisco Gentil, Centro de Lisboa, EPE (CIPM\/IPOLFG), Lisboa;"},{"name":"Instituto Gulbenkian de Ci\u00eancia, Oeiras; and"},{"name":"CEDOC, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade Nova de Lisboa, Lisboa, Portugal"}]},{"given":"T\u00e2nia","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Angiogenesis Group, Instituto Portugu\u00eas de Oncologia de Francisco Gentil, Centro de Lisboa, EPE (CIPM\/IPOLFG), Lisboa;"},{"name":"Instituto Gulbenkian de Ci\u00eancia, Oeiras; and"},{"name":"CEDOC, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade Nova de Lisboa, Lisboa, Portugal"}]},{"given":"Jacinta","family":"Serpa","sequence":"additional","affiliation":[{"name":"Angiogenesis Group, Instituto Portugu\u00eas de Oncologia de Francisco Gentil, Centro de Lisboa, EPE (CIPM\/IPOLFG), Lisboa;"},{"name":"Instituto Gulbenkian de Ci\u00eancia, Oeiras; and"},{"name":"CEDOC, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade Nova de Lisboa, Lisboa, Portugal"}]},{"given":"Cheila","family":"Torre","sequence":"additional","affiliation":[{"name":"Angiogenesis Group, Instituto Portugu\u00eas de Oncologia de Francisco Gentil, Centro de Lisboa, EPE (CIPM\/IPOLFG), Lisboa;"},{"name":"Instituto Gulbenkian de Ci\u00eancia, Oeiras; and"},{"name":"CEDOC, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade Nova de Lisboa, Lisboa, Portugal"}]},{"given":"S\u00e9rgio","family":"Dias","sequence":"additional","affiliation":[{"name":"Angiogenesis Group, Instituto Portugu\u00eas de Oncologia de Francisco Gentil, Centro de Lisboa, EPE (CIPM\/IPOLFG), Lisboa;"},{"name":"Instituto Gulbenkian de Ci\u00eancia, Oeiras; and"},{"name":"CEDOC, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade Nova de Lisboa, Lisboa, Portugal"}]}],"member":"234","reference":[{"issue":"2","key":"2019111722522606700_B1","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.molmed.2006.12.003","article-title":"Niche-to-niche migration of bone-marrow-derived cells.","volume":"13","author":"Kaplan","year":"2007","journal-title":"Trends Mol Med"},{"issue":"2","key":"2019111722522606700_B2","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1182\/blood-2004-11-4269","article-title":"Tie2 activation contributes to hemangiogenic regeneration after myelosuppression.","volume":"106","author":"Kopp","year":"2005","journal-title":"Blood"},{"issue":"11","key":"2019111722522606700_B3","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1038\/nm1102-1211","article-title":"Atherogenesis in perspective: hypercholesterolemia and inflammation as partners in crime.","volume":"8","author":"Steinberg","year":"2002","journal-title":"Nat Med"},{"issue":"2","key":"2019111722522606700_B4","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/0167-4889(90)90185-G","article-title":"Cellular cholesterol metabolism in mitogen-stimulated lymphocytes\u2014requirement for de novo synthesis.","volume":"1051","author":"Owens","year":"1990","journal-title":"Biochim Biophys Acta"},{"issue":"6","key":"2019111722522606700_B5","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1016\/S0022-2275(20)33509-4","article-title":"Expression of the monocyte chemoattractant protein-1 receptor CCR2 is increased in hypercholesterolemia. 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