{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T11:27:42Z","timestamp":1790681262151,"version":"4.1.0"},"reference-count":10,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:sec>\n            <jats:title>Background and Purpose\u2014<\/jats:title>\n            <jats:p>Low levels of low-density lipoprotein-cholesterol (LDL-C) are suspected to be associated with a risk of hemorrhagic transformation after ischemic stroke. We assessed the risk of hemorrhagic transformation after cerebral ischemia\/reperfusion in mice with low levels of LDL-C resulting from proprotein convertase subtilisin kexin 9 (PCSK9) deficiency.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods\u2014<\/jats:title>\n            <jats:p>\n              PCSK9\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              and PCSK9\n              <jats:sup>+\/+<\/jats:sup>\n              mice were fed with a high-fat\/high-cholesterol (21%\/0.15%) diet for 1 month. Plasma lipids were measured using colorimetric assays. PCSK9\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              and PCSK9\n              <jats:sup>+\/+<\/jats:sup>\n              mice (n=15 per group) were subjected to a 4-hour intraluminal occlusion of the middle cerebral artery followed by 20 hours of reperfusion. Spontaneous hemorrhagic transformation was assessed by quantification of hemoglobin in ischemic tissue. In vitro, a cell model of blood\u2013brain barrier was used to test endothelial barrier integrity in response to decreasing concentrations of LDL-C from 1 to 0.25g\/L in ischemia\/reperfusion conditions.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results\u2014<\/jats:title>\n            <jats:p>\n              PCSK9\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice had lower LDL-C, high-density lipoprotein-cholesterol, and total cholesterol levels than PCSK9\n              <jats:sup>+\/+<\/jats:sup>\n              mice before and after 1 month on the high-fat\/high-cholesterol diet. Hemoglobin concentration in ischemic cerebral tissue was not different between PCSK9\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              and PCSK9\n              <jats:sup>+\/+<\/jats:sup>\n              mice (31.5 [18.9\u201360.1] and 32.8 [14.7\u201369.9] ng\/mg protein, respectively;\n              <jats:italic>P<\/jats:italic>\n              =0.81). Infarct volume was also similar in both groups (\n              <jats:italic>P<\/jats:italic>\n              =0.66). Incubation of human cerebral endothelial cells with decreasing concentrations of LDL-C under ischemia\/reperfusion conditions did not alter blood\u2013brain barrier permeability.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Low levels of LDL-C did not increase the risk of hemorrhagic transformation after cerebral ischemia\/reperfusion in mice. Our observations suggest that PCSK9 inhibition, leading to LDL-C lowering, should not increase hemorrhagic complications after acute ischemic stroke.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/strokeaha.114.005958","type":"journal-article","created":{"date-parts":[[2014,8,15]],"date-time":"2014-08-15T04:04:25Z","timestamp":1408075465000},"page":"3086-3088","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Low Levels of Low-Density Lipoprotein-C Associated With Proprotein Convertase Subtilisin Kexin 9 Inhibition Do Not Increase the Risk of Hemorrhagic Transformation"],"prefix":"10.1161","volume":"45","author":[{"given":"Alexy","family":"Tran-Dinh","sequence":"first","affiliation":[{"name":"From the Inserm UMR1148, Paris7 University, Xavier Bichat Hospital, Paris, France (A.T.-D., A.L., L.L., C.J., O.M., P.A.); Paris 7 University, Universit\u00e9 Paris Diderot, Paris, France (A.T.-D., P.A.); CHU Bichat Stroke Center, Paris, France (P.A.); CHU de La R\u00e9union, Saint-Pierre, France (O.M.); Paris 13 University, Villetaneuse, France (A.L.); UMR PhAN Laboratory, Nantes, France (G.L.); and University of Nantes Medical School, Nantes, France (G.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang\u00e9lique","family":"Levoye","sequence":"additional","affiliation":[{"name":"From the Inserm UMR1148, Paris7 University, Xavier Bichat Hospital, Paris, France (A.T.-D., A.L., L.L., C.J., O.M., P.A.); Paris 7 University, Universit\u00e9 Paris Diderot, Paris, France (A.T.-D., P.A.); CHU Bichat Stroke Center, Paris, France (P.A.); CHU de La R\u00e9union, Saint-Pierre, France (O.M.); Paris 13 University, Villetaneuse, France (A.L.); UMR PhAN Laboratory, Nantes, France (G.L.); and University of Nantes Medical School, Nantes, France (G.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Lambert","sequence":"additional","affiliation":[{"name":"From the Inserm UMR1148, Paris7 University, Xavier Bichat Hospital, Paris, France (A.T.-D., A.L., L.L., C.J., O.M., P.A.); Paris 7 University, Universit\u00e9 Paris Diderot, Paris, France (A.T.-D., P.A.); CHU Bichat Stroke Center, Paris, France (P.A.); CHU de La R\u00e9union, Saint-Pierre, France (O.M.); Paris 13 University, Villetaneuse, France (A.L.); UMR PhAN Laboratory, Nantes, France (G.L.); and University of Nantes Medical School, Nantes, France (G.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliane","family":"Louedec","sequence":"additional","affiliation":[{"name":"From the Inserm UMR1148, Paris7 University, Xavier Bichat Hospital, Paris, France (A.T.-D., A.L., L.L., C.J., O.M., P.A.); Paris 7 University, Universit\u00e9 Paris Diderot, Paris, France (A.T.-D., P.A.); CHU Bichat Stroke Center, Paris, France (P.A.); CHU de La R\u00e9union, Saint-Pierre, France (O.M.); Paris 13 University, Villetaneuse, France (A.L.); UMR PhAN Laboratory, Nantes, France (G.L.); and University of Nantes Medical School, Nantes, France (G.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00e9ment","family":"Journ\u00e9","sequence":"additional","affiliation":[{"name":"From the Inserm UMR1148, Paris7 University, Xavier Bichat Hospital, Paris, France (A.T.-D., A.L., L.L., C.J., O.M., P.A.); Paris 7 University, Universit\u00e9 Paris Diderot, Paris, France (A.T.-D., P.A.); CHU Bichat Stroke Center, Paris, France (P.A.); CHU de La R\u00e9union, Saint-Pierre, France (O.M.); Paris 13 University, Villetaneuse, France (A.L.); UMR PhAN Laboratory, Nantes, France (G.L.); and University of Nantes Medical School, Nantes, France (G.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Meilhac","sequence":"additional","affiliation":[{"name":"From the Inserm UMR1148, Paris7 University, Xavier Bichat Hospital, Paris, France (A.T.-D., A.L., L.L., C.J., O.M., P.A.); Paris 7 University, Universit\u00e9 Paris Diderot, Paris, France (A.T.-D., P.A.); CHU Bichat Stroke Center, Paris, France (P.A.); CHU de La R\u00e9union, Saint-Pierre, France (O.M.); Paris 13 University, Villetaneuse, France (A.L.); UMR PhAN Laboratory, Nantes, France (G.L.); and University of Nantes Medical School, Nantes, France (G.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Amarenco","sequence":"additional","affiliation":[{"name":"From the Inserm UMR1148, Paris7 University, Xavier Bichat Hospital, Paris, France (A.T.-D., A.L., L.L., C.J., O.M., P.A.); Paris 7 University, Universit\u00e9 Paris Diderot, Paris, France (A.T.-D., P.A.); CHU Bichat Stroke Center, Paris, France (P.A.); CHU de La R\u00e9union, Saint-Pierre, France (O.M.); Paris 13 University, Villetaneuse, France (A.L.); UMR PhAN Laboratory, Nantes, France (G.L.); and University of Nantes Medical School, Nantes, France (G.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/MOL.0b013e328361f62d"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20882"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-022613-090402"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000252799.64165.d5"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1159\/000229781"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)15692-4"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.112.667832"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2008.12.020"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2012.206"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.04-3458fje"}],"updated-by":[{"DOI":"10.1161\/str.0000000000000043","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2014,10,1]],"date-time":"2014-10-01T00:00:00Z","timestamp":1412121600000}}],"container-title":["Stroke"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/STROKEAHA.114.005958","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T14:11:42Z","timestamp":1715609502000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/STROKEAHA.114.005958"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,10]]},"references-count":10,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2014,10]]}},"alternative-id":["10.1161\/STROKEAHA.114.005958"],"URL":"https:\/\/doi.org\/10.1161\/strokeaha.114.005958","relation":{"correction":[{"id-type":"doi","id":"10.1161\/STR.0000000000000043","asserted-by":"object"}]},"ISSN":["0039-2499","1524-4628"],"issn-type":[{"value":"0039-2499","type":"print"},{"value":"1524-4628","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,10]]},"assertion":[{"value":"2014-04-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-07-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-08-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}