Effect of Intensive Atorvastatin Therapy on Prostaglandin E2 Levels and Metalloproteinase-9 Activity in the Plasma of Patients With Non-ST-Elevation Acute Coronary Syndrome - 08/08/11
Corresponding author: Tel: 34-91-5504816; fax 34-91-5497033.Résumé |
Inflammation plays a pivotal role in the pathophysiology of non–ST elevation acute coronary syndromes (NSTEACS). Intensive statin therapy reduces the recurrence of cardiovascular events after acute coronary syndromes. The aim of this study was to examine nuclear factor–κB activity in peripheral blood mononuclear cells, prostaglandin E2 (PGE2) and leukotriene B4 levels, and matrix metalloproteinase–9 (MMP-9) activity in plasma from patients with NSTEACS (at 0 days, 4 days, 2 months, and 6 months), patients with stable coronary artery disease, and healthy controls. On day 4, patients with NSTEACS were randomized to receive atorvastatin 80 mg/day (n = 14) or standard treatment (n = 16) during 2 months to study its effect on these parameters. Nuclear factor–κB activity (by electrophoretic mobility shift assay), PGE2 levels (by enzyme-linked immunosorbent assay), and MMP-9 activity (by gelatin zymography) in the plasma of patients with NSTEACS were significantly increased compared with patients with coronary artery disease and healthy controls. At 6 months, MMP-9 activity was normalized, whereas nuclear factor–κB activity and PGE2 levels were still increased. Leukotriene B4 plasma levels (by enzyme-linked immunosorbent assay) were similar in patients with NSTEACS and those with coronary artery disease but were significantly higher than those of healthy subjects. There was a significant correlation between plasma PGE2 levels and MMP-9 activity in patients with NSTEACS (r = 0.754, p <0.01). Atorvastatin 80 mg/day reduced circulating PGE2 levels (median 222.4 [interquartile range 157.4 to 253.5] vs 550.8 [276.9 to 613.0] pg/ml, p = 0.006) and MMP-9 activity (0.0025 [0.0017 to 0.0035] vs 0.0280 [0.0057 to 0.0712] arbitrary units, p = 0.03). In conclusion, nuclear factor–κB activity in peripheral blood mononuclear cells, and plasma PGE2 levels and MMP-9 activity, increase during NSTEACS. Atorvastatin 80 mg/day normalizes PGE2 levels and MMP-9 activity, providing additional mechanisms by which intensive atorvastatin therapy may reduce the incidence of cardiovascular events.
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| This study was supported by Grants PI050451, PI052475, and PI051043 from Fundación Española del Corazón, Fondo de Investigaciones Sanitarias; Grant SAF2007/63648 from Fundación Ramón Areces, Madrid, Spain; Sociedad Española de Arteriosclerosis, Barcelona, Spain; Spanish Ministerio de Ciencia y Tecnología; Grant S2006/GEN-0247 from Comunidad Autónoma de Madrid; and Pfizer, Madrid, Spain. |
Vol 102 - N° 1
P. 12-18 - juillet 2008 Retour au numéro
Article précédent
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