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)

There is evidence for the presence of lysophosphatidylcholine (lysoPC) in oxidatively modified low density lipoprotein, human plasma and in atherosclerotic lesions. We studied the effect of lysoPC on the cytokine production by human monocytes. Among all the cytokines tested (IL-8, TNF alpha, MCP-1 and IL-1beta), we found that lysoPC most consistently stimulated human monocytes to produce IL-1beta in a dose and time dependent manner. Adherent monocytes were exposed to lysoPC in cell culture medium containing 0.5% bovine serum albumin. When exposed to lysoPC from 12.5 to 75 microM, the cellular content of IL-1beta increased 2-4 fold. Up to a concentration of 50 microM no cytotoxic effect could be seen. Over 50 microM there was evidence of toxicity. The level of IL-1beta reached its highest level at 24 h and then declined. At 48 h, the cell associated IL-1beta was low, but still the lysoPC stimulated cells produced 4.1 times more IL-1beta than controls. Also the IL-1beta mRNA was augmented by lysoPC in parallel with the IL-1beta protein levels. The stimulatory effect of lysoPC was dependent on its chain length. There was no effect on IL-1beta production when the acyl chain was shorter than 16. We also found that saturated lysoPC 18:0 stimulated IL-1beta production more than the monounsaturated lysoPC 18:1. Thus, the lysoPC in oxidatively modified LDL may stimulate the production of IL-1beta in macrophages, which may contribute to the inflammatory response in atherosclerotic tissue.
Atherosclerosis 1998 Apr
PMID:Lysophosphatidylcholine induces the production of IL-1beta by human monocytes. 962 78

Advanced glyco-oxidation end products (AGEs) generate oxygen free radicals that potentiate the development of atherosclerosis. Thus, AGEs may potentiate the aggregation of human platelets through oxidative stress. AGE-bovine serum albumin (BSA) and AGE-poly-L-lysine were evaluated for aggregation of human platelets. Superoxide in platelet-rich plasma (PRP) was measured using lucigenin-derived chemiluminescence. The platelet aggregation induced by ADP or U46619 was potentiated by preincubation with AGE-BSA, by 40% and by 59%, P < .05, respectively, vs BSA. Aggregation was increased by AGEs in a dose-dependent manner. The production of superoxide was significantly greater in PRP incubated with AGE-BSA vs BSA. The other Maillard reaction products, such as Amadori-, pentosidine-, and carboxymethyl lysine (CML)-BSA had no effect. Superoxide dismutase or indomethacin abolished the enhancing effect of AGEs on the platelet aggregation. AGEs potentiate platelet aggregation possibly with superoxide anions and prostanoids. AGE-induced potentiation of platelet aggregation may be involved in the development of atherosclerosis.
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PMID:Increased aggregation of human platelets produced by advanced glycation end products in vitro. 967 28

Serum lipoproteins including lipoprotein(a), Lp(a), are emerging as possible biological markers for cerebrovascular disease. Existing data on Lp(a) and serum lipids levels following acute ischemic stroke (AIS) are however equivocal. To determine whether serum Lp(a) and other lipid levels obtained within 24 h of acute ischemic stroke onset changed over the ensuing 4 weeks and whether these levels are related to an acute phase response, acquired nutritional deficiency, and neurovascular data, we conducted repeated measurement analyses among 19 subjects (mean age 65.0 +/- 12.1 years; 32% women) presenting with AIS (evaluated within 9.7 +/- 12.7 h). Eleven of the subjects had a moderate-to-severe stroke, defined by NIH stroke severity scale, and seven patients had a large cerebral infarction. Seven serial measurements of Lp(a), total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and other lipoproteins, major acute phase reactants and albumin levels were collected for each subject over 4 weeks. The mean initial levels, (mg/dl), of total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, Lp(a), apolipoproteins A-I and B were: 225 +/- 57.6, 154 +/- 56.0, 40 +/- 10.4, 181 +/- 93.7, 52 +/- 28.6, 130 +/- 24.6, and 141 +/- 46.1, respectively. There were no significant changes in mean serum lipid, apolipoprotein or Lp(a) levels over the 4-week study period, analyzed by a random effects model to test for time trend. In addition, there were no significant changes in established acute phase or nutritional markers (C-reactive protein, alpha 1-glycoprotein, haptoglobin or serum albumin). Our findings suggest that serum lipid, apolipoprotein and Lp(a) levels remain stable following AIS, consistent with the absence of acute phase response or nutritional deficiency.
Atherosclerosis 1998 Aug
PMID:Lipid and lipoprotein levels remain stable in acute ischemic stroke: the Northern Manhattan Stroke Study. 971 47

Glycated proteins, including serum albumin, may be involved in the pathogenesis of diabetic vasculopathy. Recent evidence suggests that expression of inducible nitric oxide synthase (iNOS) in vascular smooth muscle cells (VSMC) may, in part, promote atherosclerosis by increasing local oxidative stress. We therefore investigated whether VSMC exposed to glycated human serum albumin (GHSA) produce nitric oxide (NO) by increasing iNOS expression through transcriptional activation of the iNOS gene and whether this process is dependent on nuclear factor kappaB (NF-kappaB) activation. Treatment of VSMC with GHSA causes activation of NF-kappaB and the iNOS promoter. Induction of NF-kappaB and the iNOS promoter by GHSA exhibited dose-dependent kinetics at concentrations ranging from 3 to 1000 microgram/ml. GHSA alone was a weak inducer of NO production in VSMC as measured by determining nitrite levels, and interferon-gamma alone was totally ineffective, whereas the combination of GHSA and interferon-gamma was a strong stimulus. This synergy for NO production corresponded to Northern blot analyses of iNOS mRNA expression. Thus, GHSA may promote atherosclerosis in part by activation of NF-kappaB and upregulation of iNOS, thereby fostering local inflammation and oxidative stress.
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PMID:Glycated serum albumin-induced nitric oxide production in vascular smooth muscle cells by nuclear factor kappaB-dependent transcriptional activation of inducible nitric oxide synthase. 1033 27

It has been suggested that chronic infection with Helicobacter pylori (H. pylori), in particular infection with virulent strains producing the cytotoxin-associated protein CagA, may increase the risk of coronary heart disease by generation of a persistent low-grade inflammatory stimulus. We assessed the relation between serological markers of H. pylori infection and various markers of systemic inflammation in a population-based sample of 1834 men and women aged 18-88. A total of 39.3% of the sample had a positive IgG response, and among these a slight majority was CagA positive. Infection with H. pylori was unrelated to C-reactive protein and the leukocyte count, regardless of CagA status. There was an inverse relation between H. pylori infection and serum albumin. The adjusted OR (95% CI) of an albumin level in the bottom versus the top third were 2.2 (1.5-3.1) and 2.0 (1.4-3.1) for infection with CagA-positive and CagA-negative H. pylori strains, respectively. These results do not support the hypothesis that chronic infection with virulent H. pylori strains provokes major systemic inflammation. The mechanisms underlying the inverse association between H. pylori infection and serum albumin and the clinical relevance of this finding require further research.
Atherosclerosis 1999 Dec
PMID:Chronic infection with Helicobacter pylori does not provoke major systemic inflammation in healthy adults: results from a large population-based study. 1055 26

Heat shock proteins are a family of approximately 25 highly conserved proteins upregulated in response to various forms of stress. They play an active role in the development autoimmune diseases in animals, and have been incriminated in human autoimmune diseases (i.e. rheumatoid arthritis, multiple sclerosis). It has been previously shown, that an induced immune response against Heat shock protein 65 (HSP-65) results in atherosclerotic lesions in normocholesterolemic rabbits. We have supported these findings showing that C57BL/6 mice immunized with HSP-65 and fed a high-fat diet develop enhanced fatty streaks. To create a model that will eliminate the need for exogenous supplementation of a high-fat diet, we have immunized LDL receptor deficient (LDL-RD) mice with HSP-65 or with heat-killed Mycobacterium tuberculosis (Mt). Seven groups of LDL-RD mice (n=10), were immunized subcutaneously with different concentrations of HSP-65, Mt or bovine serum albumin (BSA). All mice were fed a normal chow-diet for 3 months. The mice immunized with the higher doses of Mt developed significantly larger fatty streaks when compared with their BSA immunized littermates. The size of the lesions in the aortic sinus were: 31,562+/-5,994 microm(2)in the 10 microg Mt and 52,777+/-5,245 microm(2)in the 100 microg Mt vs. 11, 500+/-3,750 microm(2)in the BSA group (P<0.05). In the HSP-65-immunized mice, only the group injected with the highest dose (5 microg, twice) developed significantly larger fatty streaks when compared with the BSA-immunized group (28,611+/-4,716 microm(2)vs. 11,500+/-3,750 microm(2)respectively, (P<0.05). The HSP-65-but not the Mt- or BSA-immunized mice developed high titers of anti HSP-65 antibodies, beginning 10 days after the immunization, which persisted until they were killed. Immunohistochemical staining showed CD3-positive lymphocytes in the aortic sinus of mice immunized with Mt or HSP-65, but not in the control group. Thus, we established a mouse model of HSP-65 immune mediated atherosclerosis devoid of high fat diet supplementation. This model will enable us to further study the role of the immune system in atherosclerosis, via HSP-65 and raise novel immunomodulatory therapeutic modalities.
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PMID:Immunization of low-density lipoprotein receptor deficient (LDL-RD) mice with heat shock protein 65 (HSP-65) promotes early atherosclerosis. 1067 42

Various studies have reported an inverse association between serum albumin level and incident coronary heart disease (CHD), though biologic mechanisms have not been established. The authors examined the association between serum albumin level and CHD in the Atherosclerosis Risk in Communities cohort, comprising 14,506 White and African-American middle-aged men and women. The mean albumin level in this population was 3.9 g/dl (standard deviation 0.3). During 5.2 years of follow-up, 470 incident CHD events occurred. The hazard ratio for incident CHD associated with a 1-standard deviation decrease in serum albumin level was 1.26 (95% confidence interval (CI): 1.15, 1.38) after adjustment for age, gender, and ethnicity and 1.18 (95% CI: 1.07, 1.30) after additional adjustment for covariates related to CHD. Hazard ratios were similar across gender and ethnic groups. However, there was statistically significant effect modification by smoking status, with hazard ratios of 1.01 (95% CI: 0.84, 1.22) among never smokers, 1.09 (95% CI: 0.92, 1.30) among former smokers, and 1.35 (95% CI: 1.17, 1.54) among current smokers. Further adjustment for factors related to renal disease, nutrition, platelet aggregation, inflammation, use of angiotensin-converting enzyme inhibitors, and hemostasis factors attenuated the albumin-CHD relation only slightly. In this study, serum albumin was inversely associated with incident CHD at the baseline examination in current smokers but not in never or former smokers. Albumin level may be a marker of susceptibility to the inflammatory response that results from smoking.
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PMID:Serum albumin level as a predictor of incident coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) study. 1070 15

The biological effects of Amadori adducts that are early nonenzymatically glycated protein on vascular cells were poorly defined. We examined the effect of glycated serum albumin (GA) on the expression of monocyte chemoattractant protein-1(MCP-1) that is an important chemokine recruiting monocyte to blood vessel. GA increased MCP-1 mRNA expression with a peak after 3 h of stimulation. The induction of MCP-1 by GA was dose-dependent. The MCP-1 mRNA expression by GA was completely inhibited by PD98059 and genistein that inhibit mitogen activated protein (MAP) kinase kinase and tyrosine kinase, respectively. N-Acetylcysteine, a potent antioxidant, also suppressed the GA-induced MCP-1 expression. These results suggest that GA induces production of reactive oxygen species and activates tyrosine kinase and MAP kinase in VSMC. Activation of these signals results in MCP-1 expression. GA-induced MCP-1 expression may be one of the mechanisms by which the diabetic patients suffer from accelerated atherosclerosis.
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PMID:Expression of monocyte chemoattractant protein-1 by nonenzymatically glycated albumin (Amadori adducts) in vascular smooth muscle cells. 1072 Apr 73

The toxicity of hypochlorous acid (HOCl) generated from activated neutrophils has been associated with several pathological processes such as atherosclerosis. Formation of 3-chlorotyrosine (Cl-Tyr) has been used as a marker for assessing the involvement of HOCl in such processes. In this study, we aimed to investigate the formation of Cl-Tyr from reaction of HOCl with tyrosine (both free and peptide-bound) and the fate of Cl-Tyr under such conditions. Tyrosine, N-acetyltyrosine, bovine serum albumin, and human low density lipoproteins were incubated with a range of reagent hypochlorite concentrations for varying periods in 10 mM phosphate buffer (pH 7.4) at 22 degrees C. The reaction products, and several biological samples, were hydrolyzed (in the case of proteins), isolated, and purified by high pressure liquid chromatography and characterized or quantitated by mass spectrometry and NMR. A significant amount of 3,5-dichlorotyrosine (diCl-Tyr) was obtained from the bovine serum albumin, low density lipoprotein, and some biological samples, in addition to Cl-Tyr, indicating that Cl-Tyr competes effectively for HOCl even when tyrosine is present in great excess. Cl-Tyr and diCl-Tyr were also formed from free tyrosine but then reacted further with HOCl. This finding differs from a claim in the literature that Cl-Tyr was not formed in such a system. The further reaction products of Cl-Tyr and diCl-Tyr with HOCl were elucidated as their corresponding mono- and dichlorinated 4-hydroxyphenylacetaldehydes. These results indicate the importance of assessing other products of HOCl action in addition to Cl-Tyr.
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PMID:Reactions of hypochlorous acid with tyrosine and peptidyl-tyrosyl residues give dichlorinated and aldehydic products in addition to 3-chlorotyrosine. 1075 80

In this study, it was aimed to investigate the differences in blood lipid fractions which are important risk factors for atherosclerosis and to show how the levels of serum albumin, uric acid, ionized calcium, inorganic phosphorus change with exercises between sportsmen and sedanters. 25 sportsmen and 25 sedanters (13 male, 12 female in each group) aged 18-23 were chosen for the study. From the venous blood samples taken from the two groups, levels of serum total lipid, total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, triglyceride, albumin, uric acid, ionized calcium, inorganic phosphorus were analyzed. Student's t-test was used for the statistical analyses. There were some important changes in the levels of serum triglyceride, VLDL-cholesterol and ionized calcium of sportsmen compared to those of controls.
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PMID:Investigation of serum calcium, phosphorus, albumine uric acid and lipid parameters in sportsmen and sedanters. 1079 58


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