{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T12:07:04Z","timestamp":1761394024142},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,10,24]],"date-time":"2011-10-24T00:00:00Z","timestamp":1319414400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2011,11]]},"abstract":"<jats:p><jats:bold>BACKGROUND AND PURPOSE<\/jats:bold> Ro 11\u20101464 is a thienotriazolodiazepine previously described to selectively stimulate apolipoprotein A\u2010I (apoA\u2010I) production and mRNA level in human liver cells. Here, we studied its effects upon oral administration to human apoA\u2010I transgenic (hapoA\u2010I) mice.<\/jats:p><jats:p><jats:bold>EXPERIMENTAL APPROACH<\/jats:bold> HapoA\u2010I mice were treated for 5\u2003days with increasing doses of Ro 11\u20101464. Macrophage reverse cholesterol transport (mph\u2010RCT) was assessed by following [<jats:sup>3<\/jats:sup>H]\u2010cholesterol mobilization from pre\u2010labelled i.p. injected J774 macrophages to plasma, liver and faeces. Effects on plasma lipids, apoproteins, lecithin\u2010cholesterol\u2003:\u2003acyltransferase (LCAT) and liver enzymes, as well as on faecal excretion of cholesterol and bile salts, and on liver lipids and mRNA contents were determined.<\/jats:p><jats:p><jats:bold>KEY RESULTS<\/jats:bold> Treatment with Ro 11\u20101464 300\u2003mg\u00b7kg<jats:sup>\u22121<\/jats:sup>\u00b7day<jats:sup>\u22121<\/jats:sup> resulted in a nearly 2\u2010fold increase in plasma apoA\u2010I, a 2\u2010 to 3\u2010fold increase in the level of large sized\u2010pre\u2010\u03b2 high\u2010density lipoprotein and a 3\u2010fold selective up\u2010regulation of hepatic apoA\u2010I mRNA, but a marked decrease in all plasma lipids and LCAT activity. Mpm\u2010RCT was decreased in blood but markedly increased in faecal sterols (4\u2010fold) and bile acids (1.7\u2010fold). However, liver weight and liver enzymes in plasma were also increased, in parallel with an increase in liver cholesterol ester content (all these effect being significant).<\/jats:p><jats:p><jats:bold>CONCLUSION AND IMPLICATIONS<\/jats:bold> In this model Ro 11\u20101464 causes increased hepatic expression and plasma levels of apoA\u2010I and a suppression of LCAT, and a marked enhancement of reverse cholesterol transport, but also some symptoms of liver toxicity. The compound may therefore be a prototype for a next generation of anti\u2010atherosclerotic medicines.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2011.01376.x","type":"journal-article","created":{"date-parts":[[2011,3,31]],"date-time":"2011-03-31T00:38:32Z","timestamp":1301531912000},"page":"1642-1651","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The thienotriazolodiazepine Ro 11\u20101464 increases plasma apoA\u2010I and promotes reverse cholesterol transport in human apoA\u2010I transgenic mice"],"prefix":"10.1111","volume":"164","author":[{"given":"I","family":"Zanotti","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C","family":"Maugeais","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Pedrelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Gomaraschi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P","family":"Salgam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Calabresi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F","family":"Bernini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H","family":"Kempen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,10,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M700274-JLR200"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114558"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0797-744"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118687"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003407200"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2003.09.007"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000175751.30616.13"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2008.08.038"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.475715"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.593855"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.4.713"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000148706.15947.8a"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)64849-5"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200420361"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109883200"},{"key":"e_1_2_8_17_1","unstructured":"HellerbachJ ZellerP BinderD HromatkaO(1977).Thienotriazolodiazepines. 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