Title: Rosuvastatin increases vascular endothelial PPAR{gamma} expression and corrects blood pressure variability in obese dyslipidaemic mice
Authors: Desjardins, Fanny ×
Sekkali, Belaïd
Verreth, Wim
Pelat, Michel
De Keyzer, Dieuwke
Mertens, Ann
Smith, Graham
Herregods, Marie-Christine
Holvoet, Paul
Balligand, Jean-Luc #
Issue Date: Jan-2008
Publisher: Elsevier
Series Title: European heart journal vol:29 issue:1 pages:128-137
Abstract: Aims Statins improve atherosclerotic diseases through cholesterol-reducing effects. Whether the latter exclusively mediate similar benefits, e.g. on hypertension, in the metabolic syndrome is unclear. We examined the effects of rosuvastatin on the components of this syndrome, as reproduced in mice doubly deficient in LDL receptors and leptin (DKO). Methods and results DKO received rosuvastatin (10 mg/kg/day or 20 mg/kg/day) or saline for 12 weeks. Saline-treated DKO mice had elevated blood pressure (BP) and nitric oxide-sensitive BP variability recorded by telemetry. Compared with saline, rosuvastatin (20 mg/kg/day) had no effect on weight gain and a minor effect on plasma cholesterol. Despite incomplete correction of insulin sensitivity, rosuvastatin fully corrected BP and its variability (P = 0.01), in conjunction with upregulation of PPARgamma (but not PPARalpha) in the aortic arch. Rosuvastatin similarly increased PPARgamma (P = 0.002) and SOD1 (P = 0.01) expression in isolated endothelial cells. Both GW9662, a PPARgamma-specific antagonist, and siRNA raised against PPARgamma abrogated rosuvastatin's effect, which was reproduced in PPARgamma- (but not PPARalpha-) dependent transactivation assays. Conclusion Beyond partial improvement in insulin sensitivity, rosuvastatin normalized BP homeostasis in obese dyslipidaemic mice independently of changes in body weight or plasma cholesterol. Upregulation of PPARgamma and SOD1 in the endothelium may be involved as a unique vasculoprotective effect of statin treatment.
ISSN: 0195-668X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Atherosclerosis and Metabolism (-)
× corresponding author
# (joint) last author

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