ABSTRACT
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-kappa B 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-kappa B 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-kappa B 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-kappa B 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.
Subject(s)
Acute Coronary Syndrome/blood , Dinoprostone/blood , Heptanoic Acids/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Matrix Metalloproteinase 9/blood , Pyrroles/administration & dosage , Acute Coronary Syndrome/drug therapy , Adult , Aged , Aged, 80 and over , Atorvastatin , Electrocardiography , Female , Humans , Leukotriene B4/blood , Male , Middle Aged , NF-kappa B/blood , Treatment OutcomeABSTRACT
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