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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EPeroxisome proliferator-activated receptors (PPARs) are nuclear receptors that control the transcription of several genes involved in lipid and carbohydrate metabolism. Synthetic PPAR agonists have been shown to target some of the maladies in persons that are at extremely high risk for coronary artery disease, such as type 2 diabetes and the metabolic syndrome. These agents have clear anti-atherosclerotic effects by increasing insulin sensitivity and lowering triglyceride levels. Due to their wide-ranging effects, however, elucidation of their overall mechanism and clinical relevance remains a challenge.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Ecoronary artery disease\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Ediabetes mellitus\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EPeroxisome proliferator-activated receptors (PPARs) are nuclear receptors that control the transcription of several genes involved in lipid and carbohydrate metabolism. Synthetic PPAR agonists have been shown to target some of the maladies in persons that are at extremely high risk for coronary artery disease (CAD), such as type 2 diabetes and the metabolic syndrome. These agents have clear anti-atherosclerotic effects by increasing insulin sensitivity and lowering triglyceride levels. Due to their wide-ranging effects, however, elucidation of their overall mechanism and clinical relevance remains a challenge.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-2\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EPPARgamma impedes proliferation of VSMCs and activation of inflammatory cells\u003C\/h2\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EExcessive proliferation of vascular smooth muscle cells (VSMCs) contributes to the pathogenesis of atherosclerosis. PPARgamma is expressed and upregulated in human coronary arteries in response to injury of the arterial wall, though its role was previously unclear. Bruemmer et al (Bruemmer D. \u003Cem\u003ECirc Res\u003C\/em\u003E 2003; 93:38) showed that over expression of PPARgamma induces apoptosis of human coronary VSMCs, thus providing protection from atherosclerosis. Another study found that ligand-induced activation of PPARs is also able to induce senescence in VSMCs by inhibiting telomerase (Ogawa et al. \u003Cem\u003ECirc Res\u003C\/em\u003E 2006; 98:50). These findings support PPAR ligand therapy for the treatment of cardiovascular disease.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EInflammatory cell activation and migration is an important process in early atherogenesis. Marx et al (Marx N. \u003Cem\u003ECirculation\u003C\/em\u003E 2003; 107:1954) demonstrated that in patients with type 2 diabetes and stable CAD receiving rosiglitzone, a PPAR agonist, had decreased levels of the inflammatory marker sCD40L. Similarly, this group also found that treating patients with pioglitazone, another PPARgamma agonist, significantly reduces neointima after coronary stenting in non-diabetic CAD patients (Marx N; \u003Cem\u003ECirculation\u003C\/em\u003E 2005; 112:2792).\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EThese studies represent some of the strongest evidence to date that PPARgamma activators exhibit anti-inflammatory and anti-atherogenic properties as shown by reductions in inflammatory biomarkers, improvements in vascular function, and stabilization effects on atherosclerotic lesions. Therefore, not only do these agonists exhibit metabolic effects by decreasing lipid profiles and increasing insulin sensitivity, but they also directly influence important processes in atherogenesis.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-3\u0022\u003E\n         \u003Ch2 class=\u0022\u0022\u003EWhat are the endogenous ligands of PPARs?\u003C\/h2\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EFinally, since most PPAR agonists were happened upon by chance, comments Jorge Plutzky, Assistant Professor at Harvard Medical School in Boston, MA, one way to better understand these synthetic agonists is to ask about the nature of the endogenous ligands. Dr. Plutzky\u0027s group found that endothelial lipase limits the expression of soluble adhesion molecules that are predictive of cardiovascular risk by hydrolyzing HDL and subsequently activating PPARalpha. Currently available PPAR-alpha agonists include fibrates such as fenofibrate. Construing these pathways could lead to the development of more effective and more physiologically relevant drugs.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2006 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/6\/5\/22.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzm4wq\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}