Abstract 415: Oxidized High-Density Lipoprotein Reduces Blood Clot Firmness
Low high-density lipoprotein (HDL) levels are a risk factor for cardiovascular disease. The best established anti-atherogenic property of HDL is its role in reverse cholesterol transport. Unlike HDL, low-density lipoprotein (LDL) has atherogenic properties and these are enhanced when LDL is oxidatively modified. Oxidized lipids can be transferred from oxidized LDL (oxLDL) to HDL and then be transported to the liver. However, other properties of circulating oxidized HDL (oxHDL) are not extensively investigated. Therefore we studied the role of native HDL (nHDL) and oxHDL in hemostasis. We collected citrated blood from healthy volunteers (n=5) and examined the effects of 4 mg/ml added nHDL and oxHDL on tissue factor-induced clot formation and clot firmness using thromboelastography (ROTEM). The effects of nLDL and oxLDL were measured as a control. Lipoproteins were isolated from plasma with density-gradient ultracentrifugation and oxidized with copper sulphate. The effect on fibrin degradation was examined by thromboelastography in the presence of cytochalasin D (2.5 μg/ml) and by measuring fibrin degradation products in the serum after thromboelastography using an ELISA. The ROTEM parameters clotting time, clot formation time and α-angle, were not affected by the addition of nHDL or oxHDL. The clot firmness, measured as amplitude, reduced during the thromboelastography by the addition of oxHDL. The amplitude (±SD) at 30 minutes, at 45 minutes, and at 60 minutes decreased from 100 (±0)%, 96 (±1.8)% and 91 (±2.9)% to 63 (±24.8)%, 51 (±24.3)% and 45 (±23.5)%, respectively (p<0.05) by the addition of oxHDL but did not change by the addition of nHDL. Fibrin breakdown, as measured by clot firmness in the presence of cytochalasin D was not affected by added oxHDL. In addition, the amount of fibrin degradation products after thromboelastography was comparable between control blood and blood with added oxHDL. No effects on clot firmness were observed with nLDL and oxLDL.
In conclusion, oxHDL, but not nHDL, reduces blood clot firmness in a time-dependent manner without interfering with the clot formation. This effect does not reflect fibrinolysis but most likely involves platelets. The precise mechanism by which oxHDL reduces clot firmness has yet to be elucidated.
- © 2012 by American Heart Association, Inc.