Elevated levels of 8-iso-prostaglandin F2alpha in acute coronary syndromes are associated with systemic and local platelet activation.
BACKGROUND
Oxidative stress is an important causative factor in atherosclerosis. Isoprostanes are derivatives of arachidonate oxidized by reactive oxygen species (ROS). Oxidized lipids are markers of oxidative stress, important mediators of atherosclerosis, and activators of platelets. 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) is a stable isoprostane and reliable marker of oxidative stress in vivo.


OBJECTIVE
The aim of the study was to determine the level of oxidative stress in acute coronary syndromes (ACS) and its correlations with the para meters of hemo stasis.


METHODS
Fourty-nine patients aged 46 to 76 years, including 28 with ACS and 25 with stable coronary artery disease (CAD), were enrolled to the study. The levels of 8-iso-PGF2alpha, soluble CD40 ligand (sCD40L), P-selectin (P-sel), beta-thromboglobulin, and the thrombin-antithrombin complex (TAT) in the plasma of venous blood were determined. A microvascular injury model was also used to evaluate TAT generation and sCD40L levels in blood collected every 60 seconds at the site of standardized microvascular injury.


RESULTS
8-iso-PGF2alpha levels were significantly higher in ACS compared to CAD patients (363.2 +/-45.94 vs. 328.2 -/+31.96 pg/ml, P = 0.011) and correlated with venous plasma levels of P-sel and beta-thromboglobulin in the ACS (r = 0.66; P = 0.0005 and r = 0.62; P = 0.001, respectively) and CAD groups (r = 0.46; P = 0.02 and r = 0.49; P = 0.01, respectively). In the microvascular injury model, the maximum concentrations of sCD40L in the ACS group were associated with plasma 8-iso-PGF2alpha levels (r = 0.50, P = 0.01). No correlations between 8-iso-PGF2alpha and markers of thrombin generation in venous blood and microvascular injury model were observed.


CONCLUSIONS
Plasma levels of 8-iso-PGF2alpha are significantly higher in ACS compared with stable CAD and correlate with platelet activation.
2nd Department of Medicine, Jagiellonian University School of Medicine, Kraków, Poland. konstantys@gmail.com
Konstanty
K
Szułdrzyński
Jarosław
J
Zalewski
Andrzej
A
Machnik
Krzysztof
K
Zmudka
D054058:Acute Coronary Syndrome / Q000378:metabolism*; D000368:Aged; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000097:blood; D005260:Female; D006487:Hemostasis; D006801:Humans; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D018384:Oxidative Stress; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation; D012867:Skin / Q000293:injuries; D018709:Statistics, Nonparametric; D014680:Veins / Q000293:injuries; D014950:Wounds, Penetrating / Q000097:blood; D001620:beta-Thromboglobulin / Q000378:metabolism
D015415:Biomarkers; D019007:P-Selectin; D001620:beta-Thromboglobulin; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost