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A proposed mechanism leading to accelerated vascular disease in SLE is an imbalance between vascular damage and repair, as patients with this disease display significant abnormalities in phenotype and function of endothelial progenitor cells. In addition, individuals with SLE have a higher incidence of insulin resistance which may further contribute to the increased cardiovascular risk. This study examined the role of the peroxisome proliferator activated receptor \u03b3 agonist pioglitazone in improving endothelial function, endothelial progenitor cell numbers and functional capacity, metabolic parameters, and disease activity in the lupus-prone murine model New Zealand Black\/New Zealand White (NZB \u00d7 NZW)F1. Ten-week-old prenephritic female NZB\/NZW F1 mice were exposed to 10 or 25 mg\/kg\/day of oral pioglitazone or vehicle for 15 or 24 wk. Mice exposed to pioglitazone exhibited pronounced enhancement in endothelial-dependent vasorelaxation of thoracic aortas and in endothelial progenitor cell function, as assessed by the capacity of bone marrow-derived endothelial progenitor cells to differentiate into mature endothelial cells. Pioglitazone-treated mice showed improvement in insulin resistance, adipokine, and lipid profile. Kidneys from pioglitazone-treated mice showed significant decreases in immune complex deposition, renal inflammation, T cell glomerular infiltration, and intrarenal synthesis of TNF-\u03b1, IL-1\u03b2, and VCAM-1. These results indicate that peroxisome proliferator-activated receptor \u03b3 agonists could serve as important tools in the prevention of premature cardiovascular disease and organ damage in SLE.<\/jats:p>","DOI":"10.4049\/jimmunol.0804341","type":"journal-article","created":{"date-parts":[[2009,7,20]],"date-time":"2009-07-20T20:55:04Z","timestamp":1248123304000},"page":"2729-2740","source":"Crossref","is-referenced-by-count":52,"title":["The Peroxisome Proliferator-Activated Receptor \u03b3 Agonist Pioglitazone Improves Cardiometabolic Risk and Renal Inflammation in Murine Lupus"],"prefix":"10.1093","volume":"183","author":[{"given":"Wenpu","family":"Zhao","sequence":"first","affiliation":[{"name":"Division of Rheumatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth G","family":"Thacker","sequence":"additional","affiliation":[{"name":"Division of Rheumatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey B","family":"Hodgin","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine"},{"name":"Department of Pathology, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey H","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Randolph","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily C","family":"Somers","sequence":"additional","affiliation":[{"name":"Division of Rheumatology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subramaniam","family":"Pennathur","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Michigan , Ann Arbor, MI 48109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Kretzler","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Frank C","family":"Brosius","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana J","family":"Kaplan","sequence":"additional","affiliation":[{"name":"Division of Rheumatology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,8,15]]},"reference":[{"key":"2025032709113839600_R1","first-page":"174","article-title":"Pathogenesis of lupus nephritis: an update.","volume-title":"Nephrology","year":"2005"},{"key":"2025032709113839600_R2","first-page":"408","article-title":"Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study.","volume-title":"Am. 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