{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T17:41:59Z","timestamp":1760204519428},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["ATVB"],"published-print":{"date-parts":[[1999,6]]},"abstract":"<jats:p>\n            <jats:italic>Abstract<\/jats:italic>\n            \u2014The consistent positive correlation between triglyceride and plasminogen activator inhibitor-1 (PAI-1) levels in plasma and the fact that very low density lipoprotein (VLDL) induces secretion of PAI-1 from cultured human umbilical vein endothelial cells (HUVECs) and human hepatoblastoma cells have raised the question of whether fibrate treatment, the main effect of which is a profound lowering of plasma concentrations of VLDL, might improve fibrinolytic function by reducing the plasma levels of PAI-1. However, the findings of controlled clinical trials using various fibrate compounds have been discrepant. ECs express PAI-1 under normal conditions in humans. We therefore examined the effects of several fibrate compounds on PAI-1 expression and secretion by cultured HUVECs and the HUVEC-derived cell line EA.hy926. All fibrate compounds examined had significant effects on PAI-1 gene transcription in the EA.hy926 cells. Low concentrations of clofibric acid and bezafibrate increased PAI-1 transcription and secretion, whereas Wy-14643 increased PAI-1 synthesis in a dose-dependent way. In contrast, both fenofibric acid and gemfibrozil markedly decreased PAI-1 transcription and secretion from HUVECs and EA.hy926 cells. Thus, stimulation of the transcriptional activity of the PAI-1 gene by some fibrates is linked to increased secretion of PAI-1 protein by the cells, whereas the opposite effects occur with other fibrate compounds. Whether the different effects on PAI-1 transcription and secretion by ECs in vitro also reflect differences in treatment effects on the regulation of plasma PAI-1 activity in vivo will have to be determined in larger-scale, controlled clinical trials.\n          <\/jats:p>","DOI":"10.1161\/01.atv.19.6.1577","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T19:44:19Z","timestamp":1308339859000},"page":"1577-1581","source":"Crossref","is-referenced-by-count":25,"title":["Effects of Fibrate Compounds on Expression of Plasminogen Activator Inhibitor-1 by Cultured Endothelial Cells"],"prefix":"10.1161","volume":"19","author":[{"given":"Lennart","family":"Nilsson","sequence":"first","affiliation":[{"name":"From the Atherosclerosis Research Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiya","family":"Takemura","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per","family":"Eriksson","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders","family":"Hamsten","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit, King Gustaf V Research Institute, Department of Medicine, Karolinska Institute, Karolinska Hospital, Stockholm, Sweden."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9150(94)90090-6"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00403280"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.10.6.1067"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/atv91.12.1.1310024"},{"key":"e_1_3_2_5_2","first-page":"385","volume":"5","year":"1994","journal-title":"Blood Coagul Fibrinolysis"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.16.1.89"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0268-9499(93)90068-7"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1645040"},{"key":"e_1_3_2_9_2","first-page":"57","volume":"8","year":"1994","journal-title":"Fibrinolysis"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.16.4.511"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1657709"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.85.5.1572044"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.17.1.26"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.95.3.677"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1649642"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1648809"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.46.5.860"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001250050868"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.80.12.3734"},{"key":"e_1_3_2_20_2","unstructured":"Sambrook J Fritsch EF Maniatis T. 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