title: Atorvastatin Attenuates Bone Loss and Aortic Valve Atheroma in LDLR Mice.
abstract: Atherosclerosis and osteoporosis are the leading causes of mortality and morbidity. The objective of this study was to test this hypothesis in experimental hypercholesterolemia to determine whether statins play a protective role in this process. LDLR(-/-) mice (n = 60) were allocated to the following groups: group I (n = 20), normal diet; group II (n = 20), 0.25% (w/w) cholesterol diet (w/w), and group III (n = 20), 0.25% (w/w) cholesterol diet + atorvastatin for 48 weeks. Examination of aortic valves (AVA) and femurs for atherosclerosis and calcification markers included micro-CT, special stains, and calcein incorporation. The cholesterol diet induced bone formation in calcified AVA and an increase in macrophage infiltration. Hyperlipidemic bones expressed an increase in osteoclast cells and a decrease in bone formation. Atorvastatin reduced atherosclerosis and bone mineralization in AVA and increased mineralization within femur bones (p < 0.05). Atherosclerosis is present in hyperlipidemic bones and valves as characterized by macrophage and osteoclast infiltration, and it is attenuated by atorvastatin, which may have implications for therapy in the future.
authors.affiliation: Molecular Biology and Biochemistry, Mayo Clinic School of Medicine, Rochester, Minn., USA.
authors.forename: Nalini M
authors.initials: NM
authors.lastname: Rajamannan
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001021:Aortic Valve / Q000473:pathology; D001024:Aortic Valve Stenosis; D050197:Atherosclerosis / Q000188:drug therapy* / Q000209:etiology; D000069059:Atorvastatin / Q000627:therapeutic use*; D002114:Calcinosis; D002791:Cholesterol, Dietary; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000188:drug therapy*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy*; D058226:Plaque, Atherosclerotic; D055114:X-Ray Microtomography
chemical_list: D000924:Anticholesteremic Agents; D002791:Cholesterol, Dietary; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069059:Atorvastatin