{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T04:46:24Z","timestamp":1764045984894},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T00:00:00Z","timestamp":1233619200000},"content-version":"vor","delay-in-days":4020,"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":[[1998,2]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Oxidized low density lipoproteins (LDL) are toxic to cultured endothelial cells. Mildly oxidized LDL, characterized by relatively low levels of TBARS and only minor modifications of apoB, were obtained by using 2 experimental model systems of oxidation, namely oxidation by u.v. radiation or ferrylmyoglobin (a two electron oxidation product from the reaction of metmyoglobin with H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Toxic concentrations of mildly oxidized LDL induce apoptosis (programmed cell death) of cultured endothelial cells, as shown by typical morphological features, by the <jats:italic>in situ<\/jats:italic> TUNEL procedure and by DNA fragmentation revealed on gel electrophoresis. This apoptosis is calcium\u2010dependent and subsequent to the intense and sustained cytosolic [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> peak elicited by oxidized LDL.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Five naturally occurring phenolic compounds present in food and beverages were able to prevent, in a concentration\u2010dependent manner, the apoptosis of endothelial cells induced by oxidized LDL. Among the compounds tested, caffeic acid was the most effective. Under the conditions used, the protective effect of caffeic acid (IC<jats:sub>50<\/jats:sub> 8.3\u00b12.1\u2003\u03bcmol\u2003\u2003l<jats:sup>\u22121<\/jats:sup>) in the prevention of apoptosis induced by oxidized LDL was significantly higher than that of the other compounds tested (IC<jats:sub>50<\/jats:sub>s were 12.4\u00b13.2, 14.1\u00b14.1, 20.4\u00b14.4 and 72.6\u00b19.2\u2003\u03bcmol\u2003\u2003l<jats:sup>\u22121<\/jats:sup> for ferulic, protocatechuic, ellagic and <jats:italic>p<\/jats:italic>\u2010coumaric acids, respectively).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The anti\u2010apoptotic effect of caffeic acid results from the addition of two effects, (i) the antioxidant effect which prevents LDL oxidation and subsequent toxicity (\u2018indirect\u2019 protective effect); (ii) a \u2018direct\u2019 cytoprotective effect, acting at the cellular level.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Effective concentrations of caffeic acid acted at the cellular level by blocking the intense and sustained cytosolic [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> rise elicited by oxidized LDL.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In conclusion, phenolic acids (caffeic and ferulic acids being the most potent of the compounds tested under the conditions used) exhibit a potent cytoprotective effect of cultured endothelial cells against oxidized LDL. In addition to antioxidant effect delaying LDL oxidation, caffeic acid acts as a cytoprotective agent, probably by blocking the intracellular signalling triggered by oxidized LDL and culminating in the sustained calcium rise which is involved in oxidized LDL\u2010induced apoptosis.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (1998) <jats:bold>123<\/jats:bold>, 565\u2013573; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0701624\">10.1038\/sj.bjp.0701624<\/jats:ext-link><\/jats:p>","DOI":"10.1038\/sj.bjp.0701624","type":"journal-article","created":{"date-parts":[[2005,1,28]],"date-time":"2005-01-28T19:19:31Z","timestamp":1106939971000},"page":"565-573","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Effect of dietary phenolic compounds on apoptosis of human cultured endothelial cells induced by oxidized LDL"],"prefix":"10.1111","volume":"123","author":[{"given":"Otilia","family":"Vieira","sequence":"first","affiliation":[]},{"given":"Isabelle","family":"Escargueil\u2010Blanc","sequence":"additional","affiliation":[]},{"given":"Olivier","family":"Meilhac","sequence":"additional","affiliation":[]},{"given":"Jean\u2010Pierre","family":"Basile","sequence":"additional","affiliation":[]},{"given":"Joao","family":"Laranjinha","sequence":"additional","affiliation":[]},{"given":"Leonor","family":"Almeida","sequence":"additional","affiliation":[]},{"given":"Robert","family":"Salvayre","sequence":"additional","affiliation":[]},{"given":"Anne","family":"N\u00e8gre\u2010Salvayre","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2009,2,3]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"593","article-title":"Apoptosis: the role of the endonuclease","volume":"136","author":"Arends M.J.","year":"1990","journal-title":"Am. 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