title: Lipid-lowering therapy with statins reduces microparticle shedding from endothelium, platelets and inflammatory cells.
abstract: Hyperlipidaemia is a causal factor in the ethiopathogenesis of atherosclerosis. Statins are the cornerstone drug therapy for LDL-cholesterol (LDL-c) lowering, that exert beneficial effects beyond lipid lowering. Circulating microparticles (cMPs), microvesicles released by activated cells into the bloodstream, are markers of vascular and inflammatory cell activation with tentative role in disease progression. However, the role of statins on cMPs seems controversial. We aimed at the evaluation of the effects of lipid-lowering treatment (LLT) on cMP generation in patients in primary prevention of atherosclerosis. A case-control study was conducted in hypercholesterolaemic patients receiving LLT with statins and normocholesterolaemic controls (LLT+ and LLT-, respectively, n=37/group), matched by age, gender and LDL-c levels. cMPs were characterised by flow cytometry using annexin-V and cell-specific antibodies. In LLT+-patients overall numbers of cMPs (p<0.005) were lower than in controls. Levels of cMPs carrying parental cell markers from vascular and circulating cell origin (platelet, endothelial cell, pan-leukocyte and specific-leukocyte subsets) were significantly lower in blood of LLT+ compared to LLT--patients. Moreover, MPs from LLT+-patients had reduced markers of activated platelets (αIIbβ3-integrin), activated inflammatory cells (αM-integrin) and tissue factor. The effect of LLT on cMP shedding was found to be accumulative in years. cMP shedding associated to cardiovascular risk in LLT+-patients. In summary, at similar plasma cholesterol levels patients on statin treatment had a significant lower number of cMPs carrying markers of activated cells. These findings indicate that statins protect against vascular cell activation.
authors.affiliation: Cardiovascular Research Center, c/Sant Antoni Mª Claret 167, Barcelona, Spain. lbadimon@csic-iccc.org
authors.forename: Rosa
authors.initials: R
authors.lastname: Suades
authors.forename: Teresa
authors.initials: T
authors.lastname: Padró
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Alonso
authors.forename: Pedro
authors.initials: P
authors.lastname: Mata
authors.forename: Lina
authors.initials: L
authors.lastname: Badimon
mesh_terms: D000328:Adult; D017304:Annexin A5 / Q000097:blood; D050197:Atherosclerosis / Q000097:blood / Q000517:prevention & control; D001792:Blood Platelets / Q000187:drug effects; D016022:Case-Control Studies; D055252:Cell-Derived Microparticles / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008078:Cholesterol, LDL / Q000097:blood; D042783:Endothelial Cells / Q000187:drug effects; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000097:blood* / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007249:Inflammation / Q000097:blood / Q000188:drug therapy; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011322:Primary Prevention; D013925:Thromboplastin / Q000378:metabolism
chemical_list: D017304:Annexin A5; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D013925:Thromboplastin