{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:25:33Z","timestamp":1790796333172,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","license":[{"start":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T00:00:00Z","timestamp":1538352000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Department of Clinical and Biological Sciences of Turin University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2018,10,1]]},"abstract":"<jats:p>\n                    <jats:italic>Background<\/jats:italic>\n                    . Beside the lipid-lowering effect, statins slow the progression of atherosclerosis by exerting anti-inflammatory and platelet inhibiting effects. We investigated whether platelet inhibition by simvastatin correlates with the statin effects on lipid lowering, inflammation, oxidative stress, and endothelial and platelet activation.\n                    <jats:italic>Methods.<\/jats:italic>\n                    In hypercholesterolemic patients allocated to diet (n=20) or a 2-month treatment with diet plus 40 mg simvastatin (n=25), we evaluated platelet aggregating responses to ADP, collagen, and arachidonic acid (AA), the effect of aspirin on AA-induced aggregation, pro- and anti-inflammatory and atherogenic mediators (IL-1\n                    <jats:italic>\u03b2<\/jats:italic>\n                    , -5, -6, -7, -8, -9, -10, -12, and -13, IFN-\n                    <jats:italic>\u03b3<\/jats:italic>\n                    , IP-10, Eotaxin, and sRAGE), markers of endothelium (sE-selectin, VEGF, and MCP-1) and platelet activation (sP-selectin, sCD-40L, RANTES, and PDGF-bb), and oxidative stress (8-OH-2\u2019-deoxyguanosine).\n                    <jats:italic>Results<\/jats:italic>\n                    . After treatment, beside the improvement of lipid profile, we observed the following: a reduction of platelet aggregation to ADP (p=0.0001), collagen (p=0.0001), AA (p=0.003); an increased antiaggregating effect of aspirin in the presence of AA (p=0.0001); a reduction of circulating levels of IL-6 (p=0.0034), IL-13 (p&lt;0.0001), IFN-\n                    <jats:italic>\u03b3<\/jats:italic>\n                    (p&lt;0.0001), VEGF (p&lt;0.0001), sE-selectin (p&lt;0.0001), sCD-40L (p&lt;0.0001), sP-selectin (p=0.003), and 8-OH-2\u2019-deoxyguanosine (p&lt;0.0001); an increase of IL-10 and sRAGEs (p=0.0001 for both). LDL-cholesterol levels (i) positively correlated with IL-6, IFN-\n                    <jats:italic>\u03b3<\/jats:italic>\n                    , E-selectin, sCD-40L, 8-OH-2\u2019-deoxyguanosine, platelet aggregation to ADP, collagen, AA, and aspirin IC-50 and (ii) negatively correlated with IL-10 and sRAGE. In multiple regression analyses, LDL-cholesterol was the strongest predictor for most parameters of platelet reactivity.\n                    <jats:italic>Conclusion<\/jats:italic>\n                    . In primary hypercholesterolemia, simvastatin treatment reduced platelet activation and subclinical inflammation and improved endothelial dysfunction. LDL-cholesterol levels were the major correlate of platelet reactivity; however, other effects of statins may contribute to reducing the progression of atherosclerosis.\n                  <\/jats:p>","DOI":"10.1155\/2018\/6508709","type":"journal-article","created":{"date-parts":[[2018,10,1]],"date-time":"2018-10-01T19:35:27Z","timestamp":1538422527000},"page":"1-11","source":"Crossref","is-referenced-by-count":67,"title":["Simvastatin Effects on Inflammation and Platelet Activation Markers in Hypercholesterolemia"],"prefix":"10.1155","volume":"2018","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3201-5883","authenticated-orcid":true,"given":"Cristina","family":"Barale","sequence":"first","affiliation":[{"name":"Department of Clinical and Biological Sciences, University of Turin, Turin, 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