{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T10:24:48Z","timestamp":1773915888847,"version":"3.50.1"},"reference-count":38,"publisher":"Portland Press Ltd.","issue":"6","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,9,1]]},"abstract":"<jats:p>HHcy (hyperhomocysteinaemia) is one of the major risk factors for cardiovascular diseases. A high concentration of Hcy (homocysteine) induces endothelial dysfunction by activating endothelial oxidative stress. LOX-1 (lectin-like oxidized low-density lipoprotein receptor 1) plays a vital role in regulating the progression of atherosclerotic lesions. LOX-1 activation causes endothelial apoptosis and inflammation. The mechanism is still unclear as to whether Hcy affects human endothelial LOX-1 expression. LOX-1 expression level was confirmed by Western blotting assay in Hcy-treated endothelial cells. L-Methionine was used for HHcy induction in animals. Our results suggested that Hcy increased PKC\u03b2 (protein kinase C\u03b2) activation to enhance the LOX-1 expression level. The up-regulation of PKC\u03b2 phosphorylation subsequently causes ROS (reactive oxygen species) formation and SIRT1 (sirtuin 1) degradation through a proteasome-dependent mechanism, thereby mitigating the activity of SIRT1 by deacetylating HSF1 (heat-shock transcription factor 1). We also found that NOX2 is a key NAPDH oxidase isoform responsible for the Hcy-caused ROS formation. The overexpression of SIRT1 and HSF1 reduced the Hcy-induced LOX-1 activation. Silencing PKC\u03b2 function also reduced LOX-1 activation and endothelial apoptosis caused by Hcy. Our hypothesis was supported by analysing the data from methionine-induced HHcy-affected animals. Our data indicate a new direction for LOX-1 regulation by the modulation of the PKC\u03b2\/NAPDH oxidase\/SIRT1\/HSF1 mechanism. Our findings might provide a novel route for developing new therapeutic treatments for HHcy.<\/jats:p>","DOI":"10.1042\/cs20150127","type":"journal-article","created":{"date-parts":[[2015,5,21]],"date-time":"2015-05-21T10:00:03Z","timestamp":1432202403000},"page":"477-487","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Homocysteine facilitates LOX-1 activation and endothelial death through the PKC\u03b2 and SIRT1\/HSF1 mechanism: relevance to human hyperhomocysteinaemia"],"prefix":"10.1042","volume":"129","author":[{"given":"Ching-Hsia","family":"Hung","sequence":"first","affiliation":[{"name":"Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shih-Hung","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei-Ming","family":"Chu","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine, China Medical University, Taichung, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun-Ling","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2015,6,22]]},"reference":[{"key":"2021113010374573900_B1","doi-asserted-by":"publisher","first-page":"S227","DOI":"10.1002\/mnfr.201100147","article-title":"Coenzyme Q10 suppresses oxLDL-induced endothelial oxidative injuries by the modulation of LOX-1-mediated ROS generation via the AMPK\/PKC\/NADPH oxidase signaling pathway","volume":"55","author":"Tsai","year":"2011","journal-title":"Mol. 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