Article,

Effect of Intensive Atorvastatin Therapy on Prostaglandin E(2) Levels and Metalloproteinase-9 Activity in the Plasma of Patients With Non-ST-Elevation Acute Coronary Syndrome.

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Am J Cardiol, 102 (1): 12-8 (July 2008)

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-kappaB activity in peripheral blood mononuclear cells, prostaglandin E(2) (PGE(2)) and leukotriene B(4) 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-kappaB activity (by electrophoretic mobility shift assay), PGE(2) 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-kappaB activity and PGE(2) levels were still increased. Leukotriene B(4) 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 PGE(2) levels and MMP-9 activity in patients with NSTEACS (r = 0.754, p <0.01). Atorvastatin 80 mg/day reduced circulating PGE(2) 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-kappaB activity in peripheral blood mononuclear cells, and plasma PGE(2) levels and MMP-9 activity, increase during NSTEACS. Atorvastatin 80 mg/day normalizes PGE(2) levels and MMP-9 activity, providing additional mechanisms by which intensive atorvastatin therapy may reduce the incidence of cardiovascular events.

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