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Studies using genetic\u2010 or diet\u2010induced animal models of HHcy have demonstrated a causal relationship between HHcy and accelerated atherosclerosis. Oxidative stress and activation of proinflammatory factors have been proposed to explain the atherogenic effects of HHcy. Recently, HHcy\u2010induced endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) have been found to play a role in HHcy\u2010induced atherogenesis. This review will focus on the cellular mechanisms of HHcy in atherosclerosis from both <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> studies. The contributions of ER stress and the UPR in atherogenesis will be emphasized. Results from recent clinical trials assessing the cardiovascular risk of lowering total plasma homocysteine levels and new findings examining the atherogenic role of HHcy in wild\u2010type C57BL\/6J mice will also be discussed. \u00a9 2009 International Union of Biochemistry and Molecular Biology, Inc.<\/jats:p>","DOI":"10.1002\/biof.17","type":"journal-article","created":{"date-parts":[[2009,2,19]],"date-time":"2009-02-19T03:01:59Z","timestamp":1235012519000},"page":"120-129","source":"Crossref","is-referenced-by-count":112,"title":["Contributions of hyperhomocysteinemia to atherosclerosis: Causal relationship and potential mechanisms"],"prefix":"10.1002","volume":"35","author":[{"given":"Ji","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C.","family":"Austin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,2,18]]},"reference":[{"key":"e_1_2_11_2_2","first-page":"9","volume-title":"Homocysteine in Health and Disease","author":"Jacobsen D. 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