Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study has indicated that significant shifts in plasma, urinary, and tissue taurine and in non-taurine dialyzable amines occur in the STZ-induced diabetic rat, especially in the kidney. Taurine administration at relatively low dosage ameliorated only kidney taurine concentration. Anticipated alterations in plasma glucose and creatinine were observed but neither of these changes was affected by taurine administration. Similarly, urinary output of creatinine, glucose, and NAG increased significantly among diabetic rats, but none of these were detectably influenced by taurine. Increases in plasma triglycerides observed in STZ-induced diabetes appear to be attenuated by taurine administration, and although cholesterol concentrations were lower in taurine-treated rats, the differences were not statistically significant. These findings should encourage further studies of these effects in rats as a useful model for several complications of human diabetes including atherosclerosis, retinopathy, and nephropathy.
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PMID:Supplemental taurine in diabetic rats: effects on plasma glucose and triglycerides. 231 Jun 8

The recruitment of monocytes into the arterial wall is one of the earliest events in the pathogenesis of atherosclerosis. Since monocyte chemoattractant protein 1 (MCP-1) plays a key role in the subendothelial recruitment of monocytes, we tested whether nitric oxide (NO) modulates the expression of MCP-1 in cultured human endothelial cells. Inhibition of basal NO production by NG-nitro-L-arginine (L-NAG) upregulates endothelial MCP-1 mRNA expression (250 +/- 20%) and protein secretion. Exogenous addition of NO dose-dependently decreased MCP-1 mRNA expression and secretion. Changes in MCP-1 mRNA expression and protein secretion were paralleled by corresponding changes in chemotactic activity of cell-conditioned media for monocytes. An MCP-1 antibody reduced monocyte chemotactic activity by 85% and completely abolished the increased monocyte chemotactic activity induced by the inhibition of NO production. Elevation of endothelial cGMP levels had no significant effect on MCP-1 mRNA expression. Inhibition of basal endothelial NO production by L-NAG increased binding activity of a nuclear factor kappa B (NF-kappa B)-like transcriptional regulatory factor, whereas exogenous addition of NO decreased NF-kappa B-like binding activity during stimulation with tumor necrosis factor-alpha. Thus, NO modulates MCP-1 expression and monocyte chemotactic activity secreted by human umbilical vein endothelial cells (HUVECs) in culture. The activation of NF-kappa B-like transcriptional regulatory proteins by inhibition of NO suggests a molecular link between an oxidant-sensitive transcriptional regulatory mechanism and NO synthesis in HUVECs.
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PMID:Nitric oxide modulates the expression of monocyte chemoattractant protein 1 in cultured human endothelial cells. 775 69

Gangliosides, sialic acid-containing glycosphingolipids, accumulate in atherosclerotic vessels. Their role in the pathogenesis of atherosclerosis is unknown. Gangliosides isolated from tumor cells promote collagen-stimulated platelet aggregation and ATP secretion and enhance platelet adhesion to immobilized collagen. These activities are all mediated by ganglioside effects on the platelet integrin collagen receptor alpha2beta1. Therefore, we hypothesized that gangliosides isolated from atherosclerotic plaques would enhance platelet adhesion to immobilized collagen, a major component of the subendothelial matrix of blood vessels. Furthermore, we questioned whether this effect of atherosclerotic gangliosides might play a role in the pathogenesis of atherosclerosis. To test this hypothesis, we isolated the gangliosides from postmortem aortas of patients with extensive atherosclerotic disease and examined their effects on platelet adhesion. Samples of aortic tissue taken from areas involved with atherosclerotic plaque demonstrated accumulation of gangliosides (64.9+/-6.5 nmol/g wet weight) compared with gangliosides isolated from control normal aortic tissue taken from children who died of noncardiac causes (NAGs; 21.1+/-6.4 nmol/g wet weight). Interestingly, samples of tissue taken from diseased aortas but from areas not involved with gross plaque formation also demonstrated ganglioside accumulation (47.6+/-12.8 nmol/g wet weight). Next, the activity of each of these gangliosides on platelet adhesion to immobilized type I collagen was studied. Atherosclerotic aortic gangliosides (AAGs) as well as those isolated from grossly unaffected areas of the same aorta (UAGs) both increased platelet adhesion compared with control NAGs (OD570, 0. 37+/-0.11 and 0.29+/-0.14 versus 0.16+/-0.07, respectively; P<0.01 and P<0.05, respectively). These OD570 values corresponded to 9x10(5), 8x10(4), and 6x10(3) platelets per well after preincubation with 5 micromol/L AAG, UAG, and NAG, respectively. Increased adhesion was observed after preincubation with as little as 0.5 micromol/L AAG, and maximal adhesion was seen at 2.5 micromol/L, with a plateau extending to the highest concentration tested, 10 micromol/L. The effect of AAGs on platelet adhesion to collagen was abrogated by incubation of treated platelets with F-17 anti-alpha2 monoclonal antibody (OD570, 0.13+/-0.02). Finally, the effects of the major individual gangliosides isolated from atherosclerotic tissues, GM3 and GD3, were tested. GM3 increased adhesion to collagen (OD570, 0.415+/-0.06) as did GD3 (0.31+/-0.08). Similar to that of AAGs, the effect of both molecules was blocked by F-17 (0. 09+/-0.04 and 0.13+/-0.06, respectively). These experiments demonstrate that accumulated atherosclerotic gangliosides promote platelet adhesion to collagen, the major component of the subendothelial matrix. Furthermore, this activity is mediated by an effect of the gangliosides on the collagen-binding integrin alpha2beta1. This activity may provide a mechanism for the development of platelet thrombi at sites where atherosclerotic gangliosides accumulate and help to explain the role of platelets in the process of atherosclerotic disease progression.
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PMID:Atherosclerotic aortic gangliosides enhance integrin-mediated platelet adhesion to collagen. 1007 52

Hyaluronic acid (HA) is a straight chain glycosaminoglycan polymer composed of repeating units of the disaccharide [-D-glucuronic acid-beta1,3-N-acetyl-D-glucosamine-beta1,4-]n, and is found in vertebrates and certain microorganisms. The molecular weight of HA chains is usually equal to approximately 1-10 and MDa, n > 10(3-4), although it can exists as oligosaccharides under some physiological and pathological conditions. HA resides on the cell surface or in the extracellular space, but it also occurred inside the mammalian cells. HA is synthesized in mammals by three enzymes with polymers of varying chain length. The biological functions of HA include the maintenance of elastoviscosity of liquid connective tissues, control of tissue hydration, supramolecular assembly of proteoglycans in the extracellular matrix and besides numerous receptor-mediated functions in cell attachment, mitosis, migration, tumor development, wound healing and inflammation. The extensive repertoire of biological functions of HA corresponds to the existence of a large repertoire of HA-binding proteins (hyaladherins). Many hyaladherins contain a common structural domain, termed a Link module, which is involved in ligand binding. The most important member of the Link module superfamily is the main HA receptor, CD44. CD44 has diverse functions including not only the organization and metabolism of extracellular matrix, but also engage the cytoskeleton and co-ordinate signaling events to enable the cell responce to changes in the environment. HA has an extraordinary high rate of turnover, and at the cellular level it is considered to be degraded progressively by a series of enzymatic reactions that generate polymers of decreasing sizes. HA biological effects are known to be determined by the polymer size and depend on the cell type. For example, the native high molecular weight HA is anti-angiogenic, while its degradation products (6-20 saccharides) stimulate endothelial cell proliferation, migration and differentiation. In contrast, these fragments inhibit the proliferation of vascular smooth muscle cells, whereas high molecular weight HA promotes cell growth and migration. The dysregulation of HA metabolism is a typical feature of diabetes complications, and increased glucose level is considered to be the main cause of this phenomenon. The HA depolymerization due to the effect of free radicals and advanced glycation end products leads to the vitreous body liquefaction, and may be the reason of the proliferative retinopathy in diabetes. The enrichment of extracellular matrix with high molecular weight HA under the action of high glucose level was demonstrated for vascular smooth muscle cells, skin fibroblasts, endothelial and mesangial cells. This effect is considered to accelerate the development of atherosclerosis stimulating the proliferation of vascular smooth muscle cells, and to promote the transformation of acute wounds into chronic ulcers deepening the pathological state of dermal fibroblasts in diabetes. And, on the contrary, the accumulation of high molecular weight HA on the surface of endothelial cells may have positive value for the glycocalyx integrity. Since high molecular weight HA is known to possess the anti-inflammatory and anti-fibrotic effect, the enrichment of mesangial matrix with it may represent an endogenous mechanism to limit renal injury in diabetes. Thus, the investigation of HA metabolism in diabetes mellitus emphasizes the dependence of HA biological effects on cell type and demonstrates the importance of this molecule for tissue homeostasis.
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PMID:[Hyaluronic acid, receptor CD44, and their role in diabetic complications]. 1924 16