{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T23:14:15Z","timestamp":1775862855380,"version":"3.50.1"},"reference-count":13,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,10,6]],"date-time":"2012-10-06T00:00:00Z","timestamp":1349481600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL097074"],"award-info":[{"award-number":["HL097074"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL098526"],"award-info":[{"award-number":["HL098526"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HL098329"],"award-info":[{"award-number":["HL098329"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>HMG\u2010CoA reductase inhibitors (statins) have pleiotropic effects that are independent of cholesterol\u2010lowering, including a dose\u2010dependent effect on angiogenesis. Angiogenesis plays a critical role both in vascularization of the chronically ischemic myocardium and in stabilization of atherosclerotic plaques. Chemokines, a family of structurally\u2010related cytokine molecules, exert diverse biological functions including control of angiogenesis. The effect of statin therapy on angiogenic and angiostatic chemokines has not been evaluated extensively. We sought to test the hypothesis that, in subjects with hyperlipidemia, statin therapy influences plasma levels of angiogenic and angiostatic chemokines in a dose\u2010dependent manner.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We prospectively collected demographic, angiographic and laboratory data from subjects with a history of hyperlipidemia who were either untreated or on statin therapy. A peripheral blood sample was obtained for measurement of plasma angiogenic and angiostatic chemokines. Multivariable analysis using logistic regression was performed adjusting for the following variables: age, gender, prior myocardial infarction, and chronic administration of aspirin, clopidogrel, insulin, oral hypoglycemic agents, beta\u2010blockers and calcium channel blockers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>168 patients on statin therapy (48 on low\u2010dose, defined as &lt;10mg atorvastatin\u2010equivalent, and 120 on high\u2010dose, defined as \u226510mg atorvastatin\u2010equivalent dose) and 11 subjects from the same database who had a history of hyperlipidemia but who were not on statins were enrolled. There were no significant differences in baseline demographics, co\u2010morbidities, lipid panels, other medications, or angiographic data between the groups. The angiogenic chemokines CXCL1 and CXCL12 levels were significantly different across the groups. Median levels of CXCL1 were highest in subjects not on statin therapy. Compared to subjects either not on statin therapy or on low\u2010dose statins, those taking high\u2010dose statins had lower median values of CXCL12 (2316 [2255\u201311071], vs 2362 [2016\u201310622], vs 2189 [1968\u20132705] pg\/mL, p=0.042). On multivariate analysis, CXCL12 remained the only factor that was strongly and inversely associated with statin dose at the 95% level (p=0.011).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Compared to no therapy or low\u2010dose statin therapy, treatment with high\u2010doses of HMG\u2010CoA reductase inhibitors is associated with decreased circulating CXCL12 levels in subjects with hyperlipidemia, and CXCL12 is strongly and inversely associated with statin dose. Additional studies are needed to confirm this finding in other cohorts and to determine if high\u2010dose statins affect angiogenesis in patients.<\/jats:p><\/jats:sec>","DOI":"10.1186\/2001-1326-1-23","type":"journal-article","created":{"date-parts":[[2012,10,6]],"date-time":"2012-10-06T16:14:15Z","timestamp":1349540055000},"source":"Crossref","is-referenced-by-count":25,"title":["Dose\u2010dependent Effect of Statin Therapy on Circulating CXCL12 Levels in Patients with Hyperlipidemia"],"prefix":"10.1002","volume":"1","author":[{"given":"Will","family":"Camnitz","sequence":"first","affiliation":[{"name":"From the Department of Medicine Division of Cardiology University of Virginia PO Box 800158 Charlottesville Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie D","family":"Burdick","sequence":"additional","affiliation":[{"name":"From the Department of Medicine Division of Pulmonary Critical Care University of Virginia PO Box 800546 Charlottesville Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert M","family":"Strieter","sequence":"additional","affiliation":[{"name":"From the Department of Medicine Division of Pulmonary Critical Care University of Virginia PO Box 800546 Charlottesville Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Borna","family":"Mehrad","sequence":"additional","affiliation":[{"name":"From the Department of Medicine Division of Pulmonary Critical Care University of Virginia PO Box 800546 Charlottesville Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ellen C","family":"Keeley","sequence":"additional","affiliation":[{"name":"From the Department of Medicine Division of Cardiology University of Virginia PO Box 800158 Charlottesville Virginia USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,10,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"II","DOI":"10.1161\/01.CIR.0000131517.20177.5a","article-title":"Beneficial cardiovascular effects of statins","volume":"109","author":"Davignon J","year":"2004","journal-title":"Circulation"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/hc0602.103393"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000014081.30867.F8"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00041433-200312000-00008"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021174"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(97)00965-X"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2008.11.013"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(03)00263-8"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0909602"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn244"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2007-0785"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.162305"},{"key":"e_1_2_8_14_1","unstructured":"SchuttRC BurdickMD StrieterRM MehradB KeeleyEC: Plasma CXCL12 Levels as a Predictor of Future Stroke.Stroke2012 in press."}],"container-title":["Clinical and Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1186%2F2001-1326-1-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1186\/2001-1326-1-23","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1186\/2001-1326-1-23","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1186\/2001-1326-1-23","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T11:38:52Z","timestamp":1694000332000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1186\/2001-1326-1-23"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,10,6]]},"references-count":13,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,12]]}},"alternative-id":["10.1186\/2001-1326-1-23"],"URL":"https:\/\/doi.org\/10.1186\/2001-1326-1-23","archive":["Portico"],"relation":{},"ISSN":["2001-1326","2001-1326"],"issn-type":[{"value":"2001-1326","type":"print"},{"value":"2001-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,10,6]]},"article-number":"e23"}}