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.
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.
Vascular Research Laboratory, Fundación Jiménez Díaz and Autónoma University, Madrid, Spain.
Almudena
A
Gómez-Hernández
Eva
E
Sánchez-Galán
Mónica
M
Ortego
José Luis
JL
Martín-Ventura
Luis Miguel
LM
Blanco-Colio
Nieves
N
Tarín-Vicente
José Julio
JJ
Jiménez-Nacher
Lorenzo
L
López-Bescos
Jesús
J
Egido
José
J
Tuñón
D054058:Acute Coronary Syndrome / Q000097:blood* / Q000188:drug therapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000069059:Atorvastatin; D015232:Dinoprostone / Q000097:blood*; D004562:Electrocardiography; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D007975:Leukotriene B4 / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D016328:NF-kappa B / Q000097:blood; D011758:Pyrroles / Q000008:administration & dosage*; D016896:Treatment Outcome
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016328:NF-kappa B; D011758:Pyrroles; D007975:Leukotriene B4; D000069059:Atorvastatin; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone