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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Receptors for products of non-enzymatic glycosylation have been identified previously on activated human monocytes. In this study we have found that medium conditioned by activated human monocytes following stimulation with AGE-BSA elicited an almost 3-fold greater chemotactic response from other activated monocytes than conditioned medium obtained following stimulation with control BSA (44 +/- 13 and 16 +/- 4.6, respectively; n = 9, P less than 0.05). The response elicited from AGE-BSA alone was not statistically significant. It appears that stimulation of the cells via the AGE-receptor results in the secretion of increased levels of a chemotactic substance(s) for monocytes/macrophages. This mechanism may help to explain the pathogenesis of atherosclerosis in diabetes, as monocyte accumulation within the vessel wall is an important step in fatty streak development.
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PMID:Secretion of a chemotactic substance(s) by AGE-stimulated human monocytes. 157 34

The aim in treatment of hypertension is normalization of blood pressure. The impact of treatment of hypertension on the development of IHD depends not only on the treatment of hypertension but also on influencing other basic risk factors, i.e. hyperlipoproteinaemia and smoking. Treatment of hypertension can be and should be individual and depends on a) age, b) the level of hypertension, c) complications of hypertension and d) the presence of other diseases, in particular hyperlipoproteinaemia and diabetes mellitus. The treatment of choice in hyperlipoproteinaemia are calcium antagonists, prazosin, ACE inhibitors and beta-blockers with ISA. There is experimental evidence suggesting that calcium antagonists (in particular isradipine) but also beta-blockers suppress the progression of atherosclerosis and AGE inhibitors prevent the development of cardiac and vascular hypertrophy. Effective treatment leads to a decline in the mortality from cerebrovascular attacks--in the USA in the course of 20 years a decline by 60%--in Czechoslovakia so far the mortality from cerebrovascular disease did not change which indicates unfortunately a very poor control of hypertension in the population.
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PMID:[Treatment of hypertension and cardiovascular complications]. 182 87

In diabetic plasma, glycated albumin and glycated LDL coexist with augmented levels of peroxides, conditions frequently associated with the development of accelerated atherosclerosis. The direct interaction between irreversibly glycated albumin, LDL and oxidation have not been explored yet. We tried to elucidate whether irreversibly glycated albumin (AGE-Alb) induces changes in the chemistry and morphology of LDL particle, and if AGE-Alb has the ability to scavenge free radicals, as reported for native albumin. LDL isolated from normal (nLDL) or diabetic human subjects (dLDL) was incubated in vitro with AGE-Alb in conditions of autoxidation (37 degrees C, 24-48 h in the absence of oxidation inhibitors) or of Cu2+ induced-oxidation. The results showed that, especially in the latter condition, AGE-Alb induced marked physico-chemical modifications of both nLDL and dLDL without significant changes in the level of peroxides. Incubation with AGE-Alb decreased the cholesteryl esters/unesterified cholesterol ratio of nLDL by 30% and of dLDL by approximately 50%. Concomitantly, in oxidative conditions a marked increase (approximately 3-fold) in the lysophosphatidylcholine/phosphatidylcholine ratio of dLDL was detected. Apolipoprotein B integrity as well as the morphology of the lipoprotein particles were drastically affected. To a lesser extent, these modifications occurred also in the presence of inhibitors of oxidation at 37 degrees C, but not at 4 degrees C. The above described effects were constantly more pronounced in the case of dLDL. These results indicated that in the absence of other plasma or vascular tissue components (e.g., endothelial cells, extracellular matrix) AGE-Alb by itself induces alterations in the chemistry and morphology of LDL, especially of glycated LDL, modifications that may account for the occurrence of accelerated atherogenesis in diabetes.
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PMID:Irreversibly glycated albumin alters the physico-chemical characteristics of low density lipoproteins of normal and diabetic subjects. 782 32

Diabetes is frequently associated with cardiovascular diseases (coronary heart disease, cerebrovascular disease, peripheral vascular disease), and several risk factors have been proposed. Recent studies have strengthened the importance of chronic hyperglycemia because this modifies a variety of circulating substances including lipoproteins, and the glycosylated ones can be involved in the process of accelerating atherosclerosis. In this review, previous studies indicating the significance of glycosylated lipoproteins in the progression of atherosclerosis were overviewed. We also discussed AGE (advanced glycation end products) which may play an important role of atherogenesis in diabetes.
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PMID:[Glycosylated lipoprotein]. 785 95

Non-enzymatic protein glycosylation is the first stage of the reaction described by L.C. Maillard. When the reaction progresses beyond that stage the long half-life molecules are damaged by formation of intermolecular crosslinking. The recent discovery of pentosidine, a crosslink between lysine and arginine residues, has demonstrated that advanced Maillard reaction is accelerated in diabetic patients with severe complications. Moreover, high tissue and plasma levels of pentosidine have been found in uraemia. The formation of advanced Maillard end-products (AGE) in plasma proteins constitutes a source of cell stimulation which induces macrophages to secrete cytokines, interleukin-1 and tumoral necrosis factor. Similarly, endothelial cells are induced to increase the permeability and production of the procoagulant factor. These mechanisms are thought to play an important role in the pathogenesis of atherosclerosis, nephropathy and thromboembolic disorders of diabetes. The discovery of beneficial effects of amino-guanidine, an inhibitor of advanced Maillard reaction, in the prevention of experimental diabetic complications opens a new line of investigation and new hopes for diabetics.
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PMID:[Non-enzymatic glycosylation of proteins. Complications of diabetes mellitus, aging and kidney failure]. 824 84

Human serum albumin minimally-modified by methylglyoxal (MGmin-HSA) stimulated the synthesis and secretion of macrophage-colony stimulating factor (M-CSF) by mature human monocytes in vitro. Human serum albumin minimally-modified by glucose-derived advanced glycation endproducts (AGEmin-HSA) and human serum albumin highly-modified by glucose-derived advanced glycation endproducts (AGE-HSA) stimulated much lower secretion of M-CSF from human monocytes than did MGmin-HSA. MGmin-HSA and AGE-HSA but not AGEmin-HSA also stimulated the growth of human monocytic THP-1 cells in vitro which was inhibited by polyclonal antibodies to human M-CSF. For MGmin-HSA, the median growth stimulatory concentration EC50 value was 0.24 +/- 0.07 microM and the maximal increase in cell growth was 36% of control cell growth (n = 24). Similar induction of secretion of M-CSF from monocytes in vivo may contribute to atherosclerosis in macro- and micro-angiopathy, particularly in the development of diabetic complications.
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PMID:Synthesis and secretion of macrophage colony stimulating factor by mature human monocytes and human monocytic THP-1 cells induced by human serum albumin derivatives modified with methylglyoxal and glucose-derived advanced glycation endproducts. 894 11

Human serum albumin minimally-modified by methylglyoxal (MGmin-HSA) stimulated the synthesis and secretion of tumour necrosis factor-alpha (TNF-alpha) from human monocytic THP-1 cells in vitro. Human serum albumin minimally-modified by glucose-derived advanced glycation endproducts (AGEmin-HSA) and human serum albumin highly-modified by glucose-derived advanced glycation endproducts (AGE-HSA) stimulated markedly lower synthesis and secretion of TNF-alpha from THP-1 cells than did MGmin-HSA. The median effective concentration EC50 value of MGmin-HSA for the secretion of TNF-alpha was 5.8 +/- 0.3 microM and the maximal secretion was 0.28 +/- 0.01 ng TNF-alpha/ml (n = 12) for incubations containing 5 x 10(5) cells/ml. MGmin-HSA (0.2-2.0 microM) also stimulated chemotaxis of THP-1 cells in vitro but AGE-HSA did not in this concentration range. The EC50 value of MGmin-HSA for the chemotactic response was 0.44 +/- 0.07 microM (n = 15). Similar induction of the synthesis and secretion of TNF-alpha and chemotaxis by monocytes in response to MGmin-HSA in vivo may contribute to atherosclerosis in macro- and micro-angiopathy, particularly in the development of chronic clinical complications of diabetes mellitus.
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PMID:Synthesis and secretion of tumour necrosis factor-alpha by human monocytic THP-1 cells and chemotaxis induced by human serum albumin derivatives modified with methylglyoxal and glucose-derived advanced glycation endproducts. 929 94

Oxygen radical injury and lipid peroxidation have been suggested as major causes of cancer, atherosclerosis and the aging process. We examined in vitro the effect of garlic on H2O2-induced oxidant injury in bovine pulmonary artery endothelial cells (PAEC). After overnight preincubation with Aged Garlic Extract (AGE, from Wakunaga Pharmaceutical Co., Ltd., Japan) or S-allyl cysteine (SAC), PAEC monolayers were exposed to H2O2 for 3 h. Cell viability (MTT assay), lactate dehydrogenase (LDH) release, and lipid peroxidation (TBA-RS) were measured to assess oxidant injury. AGE (1-4 mg/ml) pretreatment significantly reduced the loss of cell viability induced by 50-100 microM of H2O2. AGE and SAC exhibited dose dependent inhibition of both LDH release and TBA-RS production induced by 50 microM of H2O2. The results show that AGE and SAC can protect vascular endothelial cells from oxidant injury. Numerous garlic compounds could be involved in the antioxidant properties of garlic, while there could be some prooxidant compounds derived from garlic. It is important to keep an array of antioxidant compounds to develop good herbal preparation, like AGE.
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PMID:[Garlic compounds protect vascular endothelial cells from oxidant injury]. 950 21

To clarify the mechanism of cellular injury through the nonenzymatic reaction of glucose with proteins, we studied the cytotoxic effect of glycated bovine serum albumin on cultured smooth muscle cells in the presence of cupric ion. Glycated proteins were prepared by incubating bovine serum albumin with 0.5 M D-glucose in 0.3 M sodium phosphate buffer at 37 degrees C for 2, 4 and 16 weeks (g-BSA-2, g-BSA-4 and g-BSA-16, respectively). Early glycation products, such as fructosamine, were formed more than two weeks after incubation. However, the immunoreactivity of glycated proteins to anti-AGE antibody was 12-fold higher in g-BSA-16 than in g-BSA-2. Both g-BSA-2 and g-BSA-16 showed a concentration-dependent cytotoxicity in smooth muscle cells in the presence of 80 microM cupric ion by an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) dye reduction assay and dye exclusion test. Flow cytometry and spectrofluorophotometry using dihydrorhodamine 123 showed that the extracellular generation of oxidants was dose-dependently enhanced with increasing concentrations of g-BSA-2 or g-BSA-16 in the presence of cupric ion. However, no difference was observed in the intracellular generation of oxidants between the presence and absence of glycated proteins by flow cytometry using 2', 7'-dichlorofluorescein diacetate. Cytotoxicity and oxidant generation were prevented by catalase and tiron, but not by superoxide dismutase or mannitol, a hydroxyl radical scavenger. These results indicate that smooth muscle cells may be damaged by reactive oxygen species which are produced extracellularly by the interaction with the early glycation products and cupric ion, and suggest that hydrogen peroxide may be a candidate for reactive oxygen species which contribute to such oxidative damage of smooth muscle cells.
Atherosclerosis 1998 Feb
PMID:Oxidative damage of vascular smooth muscle cells by the glycated protein-cupric ion system. 954 97

Diabetes mellitus is complicated with vascular disorders such as atherosclerosis (macroangiopathy) and retinopathy (microangiopathy). In macroangiopathy, AGE plays an important role in atherogesis through NF-kappa B activation, that induces VCAM-1 and MCP-1. Diabetic retinopathy is based on the microangiopathy characteristic of angiogenesis. VEGF is a key substance in the angiogenesis in the retina. VEGF is produced from retinal cells exposed to AGE, adenosine, bFGF. VEGF elictes angiogenesis and increased vascular permeability (retinal edema). I consider that AGE is the most important substance in diabetic vascular disorder. Therefore, I expect a new application for diabetic angiopathy to suppress the effect of AGE.
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PMID:[Vascular endothelial cell dysfunction in diabetes mellitus]. 1019 36


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