Regulation of endothelial cell tissue factor expression by minimally oxidized LDL and lipopolysaccharide.

Abstract

Tissue factor (TF) is the predominant physiological initiator of coagulation, and its regulation is a critical aspect of endothelial cell hemostatic function. This report describes the regulation of TF mRNA expression by two physiological agonists: minimally oxidized low-density lipoprotein (MM-LDL), which may modulate endothelial hemostatic function in atherosclerosis, and lipopolysaccharide (LPS), which is a mediator of septic shock. Northern blot analysis of total RNA from human endothelial cells exposed to either MM-LDL or LPS for varying times showed that TF mRNA increased sharply at 1 hour, peaked at 2 to 3 hours, and declined to basal levels by 6 to 8 hours after treatment. The half-life of TF mRNA in MM-LDL-and LPS-exposed endothelial cells was approximately 45 minutes and 40 minutes, respectively.

Genetic evidence for a common pathway mediating oxidative stress, inflammatory gene induction, and aortic fatty streak formation in mice.

“…The results provide new and independent evidence for the "lipoprotein oxidation hypothesis" for atherosclerosis (1). In a previous report we showed that injection of MM-LDL into mice resulted in induction of the same set of genes as feeding the atherogenic diet (20,21,42,43). These genes included M-CSF, JE, heme oxygenase, inflammatory SAA, tissue factor and KC/gro.…”

Highly electronegative LDL from patients with ST-elevation myocardial infarction triggers platelet activation and aggregation

“…L5 has proatherogenic effects similar to those of laboratory-derived oxidized LDL (ox-LDL), which, interestingly, has been shown to render the endothelium highly thrombogenic by increasing tissue factor expression 18 and EC apoptosis. 19 In addition, ox-LDL-induced endothelial dysfunction is accompanied by an increase in P-selectin and E-selectin expression on cells, resulting in increased platelet-EC interactions.…”

Oxidized low density lipoprotein inhibits lipopolysaccharide-induced binding of nuclear factor-kappaB to DNA and the subsequent expression of tumor necrosis factor-alpha and interleukin-1beta in macrophages.

“…These studies show that MM-LDL induces IL-1 ␤ in monocytes. In endothelial cells MM-LDL may induce the expression of colony stimulating factor, monocyte chemoattractant protein 1, and tissue factor (1)(2)(3)(4). In endothelial cells it has also been shown that MM-LDL induces the transcription factor nuclear factor (NF)-B to bind to its binding site on DNA (5).…”