Platelet interaction with bioactive lipids formed by mild oxidation of low-density lipoprotein

Oxidation of low-density lipoprotein (LDL) generates
pro-inflammatory and pro-thrombotic mediators that play a crucial
role in cardiovascular and inflammatory diseases. Mildly oxidized
LDL (mox-LDL) and minimally modified LDL (mm-LDL) which escape the
uptake of macrophage scavenger receptors accumulate in the
atherosclerotic intima. Oxidatively modified LDL is also present
within the electronegative LDL fraction in blood, which is elevated
in patients at high risk for cardiovascular diseases. Mox-LDL and
mm-LDL, but not native LDL are able to induce platelet shape change
and aggregation. LDL oxidation generates lipids with platelet
stimulatory properties such as lysophosphatidylcholine, certain
oxidized phosphatidylcholine molecules, F-2-isoprostanes and
lysophosphatidic acid (LPA). Mox-LDL and mm-LDL are like a Trojan
horse carrying these biologically active lipids and attacking cells
through activation of physiological receptors and signaling
mechanisms. LPA has been identified as the lipid responsible for
platelet stimulation by mox-LDL, mm-LDL and also mox-HDL. These
lipoproteins activate platelets by stimulating G-protein coupled
LPA receptors and a Rho/Rho kinase signaling pathway leading to
platelet shape change and subsequent aggregation. LPA-mediated
platelet activation might contribute to arterial thrombus formation
after rupture of atherosclerotic plaques and to the increased blood
thrombogenicity of patients with cardiovascular diseases. Copyright
(c) 2006 S. Karger AG, Basel.