Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.6 (CAD)
4,420 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One early phase of atherosclerosis involves the recruitment of inflammatory cells from the circulation and their transendothelial migration. This process is predominantly mediated by cellular adhesion molecules, which are expressed on the vascular endothelium and on circulating leukocytes in response to several inflammatory stimuli. Selectins (P, E and L) and their ligands (mainly P-selectin ligand) are involved in the rolling and tethering of leukocytes on the vascular wall. Intercellular adhesion molecules (ICAMs) and vascular cell adhesion molecules (VCAM-1), as well as some of the integrins, induce firm adhesion of inflammatory cells at the vascular surface, whereas platelet endothelial cellular adhesion molecules (PECAM-1) are involved in extravasation of cells from the blood compartment into the vessel and underlying tissue. For most of the cellular adhesion molecules, except integrins, soluble forms have been identified in the circulation although their origins are not fully understood. Several lines of evidence support a crucial role of adhesion molecules in the development of atherosclerosis and plaque instability. Expression of VCAM-1, ICAM-1 and L-selectin has been consistently observed in atherosclerotic plaques. There is accumulating evidence from prospective studies for a predictive role of elevated circulating levels of sICAM-1 in initially healthy people, and of sVCAM-1 in patients at high risk or with overt CAD. A large number of common polymorphisms has been identified in the genes encoding the different adhesion molecules, but studies investigating their relationship either with soluble forms or with CAD are still sparse and often based on small samples. Further research is needed to firmly establish the potential clinical and therapeutic utilities of (soluble) adhesion molecules, but results in both fields hold the promise that in future, adhesion molecules might add information for clinical risk prediction and serve as therapeutic targets.
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PMID:Adhesion molecules and atherosclerosis. 1461 98

Diabetes increases the risk of coronary artery disease. We examined the effects of lifestyle modification on key contributing factors to atherogenesis, including oxidative stress, inflammation and cell adhesion. Diabetic men (N=13) were placed on a high-fiber, low-fat diet in a 3-week residential program where food was provided ad libitum and daily aerobic exercise was performed. In each subject, pre- and post-intervention fasting blood was drawn for circulating levels of serum lipids, glucose and insulin, oxidative stress marker 8-isoprostaglandin F2alpha (8-iso-PGF2alpha), the inflammatory protein C-reactive protein (CRP), and soluble intracellular adhesion molecule (sICAM)-1 and sE-selectin as indicators of endothelial activation. Using subject sera and human aortic endothelial cell (HAEC) culture systems, serum-induced monocyte adhesion, ICAM-1, vascular cell adhesion molecule-1 (VCAM-1) and cell surface abundance, and monocyte chemotactic protein-1 (MCP-1) production were determined. Nitric oxide (NO), superoxide, and hydrogen peroxide production were measured in vitro by fluorometric detection. After 3 weeks, significant reductions (p<0.05) in BMI, all serum lipids including total cholesterol (pre: 188.9+/-10.1 mg/dL versus post: 146.3+/-3.8 mg/dL) and low-density lipoprotein (103.1+/-10.2 mg/dL versus 76.4+/-4.3 mg/dL), fasting serum glucose (157.5+/-10.1 mg/dL versus 126.7+/-8.7 mg/dL), insulin (33.8+/-4.0 microU/ml versus 23.8+/-3.4 microU/ml), homeostasis model assessment for insulin resistance, 8-iso-PGF2alpha, CRP, sICAM-1, and sE-selectin were noted. In vitro, serum-stimulated monocyte adhesion, cellular ICAM-1 and VCAM-1 expression (p<0.05), and fluorometric detection of superoxide and hydrogen peroxide production decreased, while a concomitant increase in NO production was noted (all p<0.01). A combination of diet and exercise ameliorates oxidative stress, inflammation, and monocyte-endothelial interaction. Intensive lifestyle modification may improve novel CAD risk factors in men with diabetes.
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PMID:Effect of a diet and exercise intervention on oxidative stress, inflammation and monocyte adhesion in diabetic men. 1661 95