| Combined effects of HMG-CoA-reductase inhibition and renin-angiotensin system blockade on experimental atherosclerosis. | |
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MedLine Citation:
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PMID: 16115475 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Therapeutic strategies to prevent atherosclerotic plaque progression and achieve plaque stabilization involve 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)-reductase inhibitors (statins) and renin-angiotensin system (RAS)-blockade, but studies investigating the potentially additive effects of a combined treatment strategy are rare. We hypothesised that the adjunction of atorvastatin with telmisartan or ramipril might achieve additional effects on experimental atherosclerosis though statin-induced lipid-lowering is lacking. ApoE-/- mice were fed a high-fat diet for 12 weeks and randomized to either placebo (CON), atorvastatin (ATO), ramipril (RAM), telmisartan (TEL) or RAM+ATO and TEL+ATO (N=23 per group). RAS-blockade, but not ATO, reduced systolic blood pressure. None of the treatment regimens lowered systemic cholesterol levels or lipoprotein fractions. RAM, TEL and the combined therapy, but not ATO, significantly reduced aortic lipid deposition. All substances significantly reduced monocyte chemoattracting protein (MCP)-1 concentrations, macrophages and matrixmetalloproteinase (MMP)-9 content and enhanced plaque's content of tissue inhibitor of MMP (TIMP)-1, collagen and fibrous cap thickness, resulting in an overall decrease of advanced plaques (classified as types IV-VI). Additive effects of the adjunction were observed on MMP-9 gelatinolytic activity, interleukin (IL)-6 and IL-10 plasma levels. These results indicate that a combined treatment with RAS-blockade and statins may have additive effects on systemic cardiovascular risk markers even in the absence of lipid-reduction, although additional effects on atherosclerotic plaque progression and stability were not observed in this model. |
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Authors:
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Christina Grothusen; Sylvia Bley; Tina Selle; Maren Luchtefeld; Karsten Grote; Uwe J F Tietge; Helmut Drexler; Bernhard Schieffer |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Atherosclerosis Volume: 182 ISSN: 0021-9150 ISO Abbreviation: Atherosclerosis Publication Date: 2005 Sep |
Date Detail:
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Created Date: 2005-08-23 Completed Date: 2006-01-12 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0242543 Medline TA: Atherosclerosis Country: Ireland |
Other Details:
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Languages: eng Pagination: 57-69 Citation Subset: IM |
Affiliation:
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Department of Cardiology and Angiology, Medizinische Hochschule Hannover, Carl Neuberg Strasse 1, 30625 Hannover, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin-Converting Enzyme Inhibitors
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pharmacology* Animals Apolipoproteins E / genetics Atherosclerosis / drug therapy*, pathology, physiopathology Benzimidazoles / pharmacology* Benzoates / pharmacology* Chemokine CCL2 / blood Disease Models, Animal Drug Therapy, Combination Heptanoic Acids / pharmacology* Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology* Immunohistochemistry Interleukin-10 / blood Interleukin-6 / blood Macrophages / pathology Male Matrix Metalloproteinase 9 / metabolism Mice Mice, Inbred C57BL Mice, Mutant Strains Monocytes / pathology Pyrroles / pharmacology* Ramipril / pharmacology Renin-Angiotensin System / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Angiotensin-Converting Enzyme Inhibitors; 0/Apolipoproteins E; 0/Benzimidazoles; 0/Benzoates; 0/Ccl2 protein, mouse; 0/Chemokine CCL2; 0/Heptanoic Acids; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Interleukin-6; 0/Pyrroles; 110862-48-1/atorvastatin; 130068-27-8/Interleukin-10; 144701-48-4/telmisartan; 87333-19-5/Ramipril; EC 3.4.24.35/Matrix Metalloproteinase 9 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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