{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:22:09Z","timestamp":1790713329374,"version":"4.1.0"},"reference-count":138,"publisher":"Portland Press Ltd.","issue":"3","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,2,1]]},"abstract":"<jats:p>The relevance of PPAR\u03b3 (peroxisome-proliferator-activated receptor \u03b3) as an important therapeutic target for the treatment of diabetes arises from its hypoglycaemic effects in diabetic patients and also from the critical role in the regulation of cardiovascular functions. From a clinical perspective, differences between current FDA (Food and Drug Administration)-approved PPAR\u03b3 drugs have been observed in terms of atherosclerosis and cardiac and stroke events. The adverse effects of PPAR\u03b3-specific treatments that hamper their cardiovascular protective roles, affirm the strong need to evaluate the efficacy of the current drugs. Therefore active research is directed towards high-throughput screening and pharmacological testing of a plethora of newly identified natural or synthetic compounds. In the present review we describe the rationale behind drug design strategies targeting PPAR\u03b3, based on current knowledge regarding the effects of such drugs in experimental animal models, as well as in clinical practice. Regarding endogenous PPAR\u03b3 ligands, several fatty acid derivatives bind PPAR\u03b3 with different affinities, although the physiological relevance of these interactions is not always evident. Recently, NO-derived unsaturated fatty acids were found to be potent agonists of PPARs, with preferential affinity for PPAR\u03b3, compared with oxidized fatty acid derivatives. Nitroalkenes exert important bioactivities of relevance for the cardiovascular system including anti-inflammatory and antiplatelet actions, and are important mediators of vascular tone. A new generation of insulin sensitizers with PPAR\u03b3 function for the treatment of diabetes may serve to limit patients from the increased cardiovascular burden of this disease.<\/jats:p>","DOI":"10.1042\/cs20080195","type":"journal-article","created":{"date-parts":[[2009,1,8]],"date-time":"2009-01-08T15:19:37Z","timestamp":1231427977000},"page":"205-218","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":103,"title":["PPAR\u03b3 and its ligands: therapeutic implications in cardiovascular disease"],"prefix":"10.1042","volume":"116","author":[{"given":"Luis","family":"Villacorta","sequence":"first","affiliation":[{"name":"Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco\u00a0J.","family":"Schopfer","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jifeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce\u00a0A.","family":"Freeman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.\u00a0Eugene","family":"Chen","sequence":"additional","affiliation":[{"name":"Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2009,1,8]]},"reference":[{"key":"2021113010123632600_B1","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1016\/S0140-6736(07)61696-1","article-title":"The burden and costs of chronic diseases in low-income and middle-income countries","volume":"370","author":"Abegunde","year":"2007","journal-title":"Lancet"},{"key":"2021113010123632600_B2","doi-asserted-by":"crossref","first-page":"50J","DOI":"10.1016\/S0002-9149(03)00616-7","article-title":"Management of diabetes mellitus and insulin resistance in patients with cardiovascular disease","volume":"92","author":"Fonseca","year":"2003","journal-title":"Am. 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