Prevention of atherosclerosis by the mTOR inhibitor everolimus in LDLR(-/-) mice despite severe hypercholesterolemia.

Prevention of atherosclerosis by the mTOR inhibitor everolimus in LDLR(-/-) mice despite severe hypercholesterolemia. Research Abstract Details 

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Prevention of atherosclerosis by the mTOR inhibitor everolimus in LDLR(-/-) mice despite severe hypercholesterolemia. Abstract Text:

Marc A Mueller,Frank Beutner,Daniel Teupser,Uta Ceglarek,Joachim Thiery,Marc A Mueller,Frank Beutner,Daniel Teupser,Uta Ceglarek,Joachim Thiery,

Everolimus inhibits the mammalian target of rapamycin (mTOR) in proliferating cells. It is widely used in transplant patients and has also been exploited by drug-eluting stents for the treatment of cardiovascular disease. However, there is only limited data on the pathophysiological effects of mTOR-inhibitors on the vascular wall. We aimed to unravel the effects of everolimus on cholesterol-induced atherosclerosis and on circulating cell mediators in LDL-receptor-deficient (LDLR(-/-)) mice. Male hypercholesterolemic LDLR(-/-) mice received either solvent (group A; n=28) or everolimus at 0.05mg/kg (group B, n=22) and 1.5mg/kg (group C, n=29) per body weight per day by subcutaneously implanted osmotic minipumps for the study period of 12 weeks. Group B showed 44% reduction of atherosclerotic lesions at the brachiocephalic artery (BCA). In group C atherosclerotic lesions were reduced by 85% in the BCA and by 60% at the aortic root. This was associated with a significantly lower complexity of lesions in both treated groups (p<0.001) and despite a 40% increase of plasma cholesterol. Everolimus caused a significant reduction of circulating cell mediators such as interleukin-1alpha, interleukin-5, GM-CSF and interleukin-12p40. Everolimus increased the plasma levels of KC but had no effect on eighteen other circulating cell mediators studied. Everolimus strongly inhibits atherosclerosis development in LDL-receptor(-/-) mice despite severe hypercholesterolemia. Everolimus application had only small effects on circulating cell mediators. The significant reduction of atherosclerotic lesions was associated with a delayed transition from early macrophages enriched lesions to advanced atherosclerotic plaques.

Prevention of atherosclerosis by the mTOR inhibitor everolimus in LDLR(-/-) mice despite severe hypercholesterolemia. Publishing Authors By Initials

MA Mueller,F Beutner,D Teupser,U Ceglarek,J Thiery,MA Mueller,F Beutner,D Teupser,U Ceglarek,J Thiery,

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Prevention of atherosclerosis by the mTOR inhibitor everolimus in LDLR(-/-) mice despite severe hypercholesterolemia. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Atherosclerosis

VOLUME: 198

Page Numbers: 39-48

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ISSN: 1879-1484

DAY: 5

MONTH: 11

YEAR: 2007

Prevention of atherosclerosis by the mTOR inhibitor everolimus in LDLR(-/-) mice despite severe hypercholesterolemia. Information

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LANGUAGE: eng

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Country: Ireland

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MEDLINETA: Atherosclerosis

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