Lysophosphatidic Acid Induction of Tissue Factor Gene Expression

LPA is a component of oxidized low density lipoproteins (oxLDL) which has been shown to accumulate in human atherosclerotic plaques. Tissue factor (TF) is the principal initiator of blood coagulation. Tissue factor upregulation in atherosclerotic plaque can lead to undesirable vascular thrombosis. The generation of reactive oxygen species (ROS), which act as signaling molecules in the vascular system, is enhanced in response to injury and has been associated with a procoagulant state and the progression of atherosclerotic disease. Oxidative stress might contribute to the increased expression of pro atherosclerotic genes at sites of vascular injury, including TF. Little is known about the regulation of TF by LPA in smooth muscle cells (SMC) which is a major player in the process of atherosclerosis. Data generated by this study demonstrate that LPA markedly induces TF expression in rat aorta smooth muscle cells (RASMCs) and human aorta smooth muscle cells (HASMCs). The signaling pathways involved are multiple.