Rosuvastatin increases vascular endothelial PPARgamma expression and corrects blood pressure variability in obese dyslipidaemic mice
| Autor: | Jean-Luc Balligand, Graham Smith, Belaid Sekkali, Wim Verreth, Fanny Desjardins, Dieuwke De Keyzer, Michel Pelat, Marie-Christine Herregods, Paul Holvoet, A. Mertens |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Statin Endothelium medicine.drug_class Mice Obese Blood Pressure Mice Internal medicine Medicine Animals Rosuvastatin Rosuvastatin Calcium Dyslipidemias Sulfonamides business.industry Leptin nutritional and metabolic diseases medicine.disease Fluorobenzenes PPAR gamma medicine.anatomical_structure Blood pressure Endocrinology Pyrimidines Receptors LDL Hypertension Metabolic syndrome Hydroxymethylglutaryl-CoA Reductase Inhibitors Cardiology and Cardiovascular Medicine business Blood vessel medicine.drug |
| Zdroj: | European heart journal. 29(1) |
| ISSN: | 0195-668X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|