Atherothrombosis: role of tissue factor; link between diabetes, obesity and inflammation.

Atherothrombotic vascular disease is a complex disorder in which inflammation and coagulation play a pivotal role. Rupture of high-risk, vulnerable plaques with the subsequent tissue factor (TF) exposure is responsible for coronary thrombosis, the main cause of unstable angina, acute myocardial infarction, and sudden cardiac death. Tissue factor (TF), the key initiator of coagulation is an important modulator of inflammation.

Inflammation and neovascularization in diabetic atherosclerosis.

Diabetes mellitus, the major cardiovascular risk factor, accentuates the inflammation and neovascularization processes leading to enhanced progression of atherosclerotic complications. Inflammation in diabetes mellitus is the key initiator of atherosclerotic process, which results in acute coronary events. Atherosclerosis evolves from the endothelial cell dysfunction and succeeding entry of hemodynamically derived leukocytes by migration, activation and production of lipid gruel leading to atheromatous plaque progression and subsequent regression.

Metabolic syndrome and diabetic atherothrombosis: implications in vascular complications.

Metabolic syndrome is characterized by the clustering of a number of metabolic abnormalities in the presence of underlying insulin resistance with a strong association with diabetes and cardiovascular disease morbidity and mortality. The disorder is defined in different ways, but the pathophysiology is attributable to insulin resistance. An increased release of free fatty acids (FFAs) from adipocytes block insulin signal transduction pathway, induce endothelial dysfunction due to increased reactive oxygen species (ROS) generation and oxidative stress.

Modification of environmental toxicity by nutrients: implications in atherosclerosis.

We hypothesize that nutrition can modulate the toxicity of environmental pollutants and thus modulate health and disease outcome associated with chemical insult. There is now increasing evidence that exposure to persistent organic pollutants, such as PCBs, can contribute to the development of inflammatory diseases such as atherosclerosis. Activation, chronic inflammation, and dysfunction of the vascular endothelium are critical events in the initiation and acceleration of atherosclerotic lesion formation.

Involvement of CYP 2C9 in mediating the proinflammatory effects of linoleic acid in vascular endothelial cells.

Objective: Polyunsaturated fatty acids such as linoleic acid are well known dietary lipids that may be atherogenic by activating vascular endothelial cells. In the liver, fatty acids can be metabolized by cytochrome P450 (CYP) enzymes, but little is known about the role of these enzymes in the vascular endothelium. CYP 2C9 is involved in linoleic acid epoxygenation, and the major product of this reaction is leukotoxin (LTX).