JOURNAL ARTICLE

Rosuvastatin restores superoxide dismutase expression and inhibits accumulation of oxidized LDL in the aortic arch of obese dyslipidemic mice

W Verreth, D De Keyzer, P C Davey, B Geeraert, A Mertens, M-C Herregods, G Smith, F Desjardins, J-L Balligand, P Holvoet
British Journal of Pharmacology 2007, 151 (3): 347-55
17384667

BACKGROUND AND PURPOSE: Our goal was to elucidate mechanisms of the inhibitory effect of rosuvastatin on the accumulation of plaque oxidized low density lipoproteins (oxLDL) and on plaque volume, without lowering cholesterol, in mice with combined leptin and LDL-receptor deficiency (DKO).

EXPERIMENTAL APPROACH: Twelve-week old DKO mice were treated with rosuvastatin (10 mg kg(-1) day(-1), s.c.) or placebo or no treatment for 12 weeks. The effect on blood variables, aortic plaque volume and composition and gene expression in the aorta and in THP-1 cells was assessed.

KEY RESULTS: Rosuvastatin lowered free fatty acids (FFA), triglycerides, and increased insulin sensitivity, without affecting cholesterol. Rosuvastatin lowered the plaque volume, inhibited macrophage, lipid and oxLDL accumulation, and decreased the oxLDL-to-LDL ratio of plaques in the aortic arch. It increased superoxide dismutase 1 (SOD1), CD36, LXR-alpha, ABCA-1 and PPAR-gamma RNA expression in aortic extracts. SOD1 was the strongest inverse correlate of oxLDL. In THP-1 macrophages and foam cells, expression of SOD1 was lower than in THP-1 monocytes. Rosuvastatin restored expression of SOD1 in THP-1 macrophages and foam cells.

CONCLUSIONS AND IMPLICATIONS: Rosuvastatin restored SOD1 expression in THP-1 macrophages and foam cells in vitro and in the aorta of DKO mice. The latter was associated with less oxLDL accumulation within atherosclerotic plaques and inhibition of plaque progression. This effect was obtained at a dose not affecting cholesterol levels but improving insulin sensitivity. SOD1 is a potentially important mediator of the prevention of oxLDL accumulation within atherosclerotic plaques.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read
17384667
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"