ABSTRACT
BACKGROUND: The clinical benefits of lipid lowering with statins are attributed to changes in plaque composition leading to lesion stability, but supporting clinical data from human studies are lacking. Therefore, we investigated the effect of 3 months of pravastatin treatment on composition of human carotid plaques removed during carotid endarterectomy. METHODS AND RESULTS: Consecutive patients with symptomatic carotid artery stenosis received 40 mg/d pravastatin (n=11) or no lipid-lowering therapy (n=13; control subjects) for 3 months before scheduled carotid endarterectomy. Carotid plaque composition was assessed with special stains and immunocytochemistry with quantitative image analysis. Plaques from the pravastatin group had less lipid by oil red O staining (8.2+/-8.4% versus 23.9+/-21.1% of the plaque area, P<0.05), less oxidized LDL immunoreactivity (13.3+/-3.6% versus 22.0+/-6.5%, P<0.001), fewer macrophages (15.0+/-10.2% versus 25.3+/-12.5%, P<0.05), fewer T cells (11.2+/-9.3% versus 24.3+/-13.4%, P<0.05), less matrix metalloproteinase 2 (MMP-2) immunoreactivity (3.6+/-3.9% versus 8.4+/-5.3%, P<0.05), greater tissue inhibitor of metalloproteinase 1 (TIMP-1) immunoreactivity (9.0+/-6.2% versus 3.1+/-3.9%, P<0.05), and a higher collagen content by Sirius red staining (12.4+/-3.1% versus 7.5+/-3.5%, P<0.005). Cell death by TUNEL staining was reduced in the pravastatin group (17.7+/-7.8% versus 32.0+/-12.6%, P<0.05). CONCLUSIONS: -Pravastatin decreased lipids, lipid oxidation, inflammation, MMP-2, and cell death and increased TIMP-1 and collagen content in human carotid plaques, confirming its plaque-stabilizing effect in humans.
Subject(s)
Carotid Artery Diseases/therapy , Collagen/metabolism , Lipid Metabolism , Metalloendopeptidases/metabolism , Pravastatin/therapeutic use , Aged , Apolipoprotein B-100 , Apolipoproteins B/metabolism , Carotid Arteries/metabolism , Carotid Arteries/pathology , Carotid Artery Diseases/metabolism , Carotid Artery Diseases/pathology , Carotid Artery Diseases/prevention & control , Cell Adhesion Molecules/metabolism , Cell Death/drug effects , Cholesterol/blood , Disease Progression , Endarterectomy, Carotid , Female , Humans , In Situ Nick-End Labeling , Inflammation/drug therapy , Inflammation/prevention & control , Lipoproteins/blood , Male , Matrix Metalloproteinase 2/metabolism , Middle Aged , NF-kappa B/metabolism , Prospective Studies , Sweden , Tissue Inhibitor of Metalloproteinases/metabolism , Treatment OutcomeABSTRACT
Pasteurella multocida is a frequent cause of infection after animal bites. In contrast to earlier reports, P. multocida appeared to be as common among dogs as among cats. We found 17 (81%) of 21 pet dogs to harbour P. multocida in their saliva. At normal contact, the risk of transmission from dogs to humans seems to be negligible. Only 1/27 dogs owners was found to harbour the organism. None of 13 cat owners or 23 persons without animal contacts harboured P. multocida.
