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)

Population kinetics of monocytes (MC) was studied to prove their participation in atherogenesis. Increased number of cells containing lipids (CCL) in patients with severe stable angina pectoris is demonstrated (42.5 versus 7.4% in healthy persons). This is followed by MC esterase activity enhancement. In patients with angina of effort new types of MC appear (with high peroxidase and low esterase activity) and there is a drastic increase of CCL (more than 56%). The correlation between the number of CCL and indices of blood lipid metabolism in anginal patients is lacking. The results obtained may serve as a criterion for evaluating the degree and exacerbation of coronary atherosclerosis in humans.
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PMID:[Population kinetics of circulating monocytes in health and in patients with ischemic heart disease]. 831 11

The capacity of macrophages to influence directly and indirectly fibrinolytic processes in atherosclerosis was studied using macrophages isolated from atherosclerotic plaques of patients undergoing surgical repair of distal aortic and femoral arteries. These cells were characterized by their morphology, adherence, esterase positivity, and expression of CD14 antigen. Production of plasminogen activator inhibitor type-1 (PAI-1) by plaque macrophages (6.7 +/- 2.7 ng/10(5) cells/24 hours [mean +/- SEM]) was significantly greater than PAI-1 production by blood monocytes isolated simultaneously from the same patients (1.8 +/- 1.5 ng/10(5) cells/24 hours). Production of tissue type plasminogen activator and urokinase type was not augmented compared to blood monocytes. Conditioned medium from cultured plaque macrophages significantly increased production of PAI-1 by endothelial cells (85 +/- 11% above basal) and vascular smooth muscle cells (25 +/- 10%) in vitro. This response was significantly greater than the response to monocyte-conditioned medium (endothelial cells 38 +/- 11%, vascular smooth muscle cells 2.5 +/- 2.0%). Stimulation of endothelial cell PAI-1 production by macrophage-conditioned medium was partially inhibitable by a monoclonal antibody to transforming growth factor-beta. Tissue type plasminogen activator production by endothelial cells and vascular smooth muscle cells was not affected by plaque macrophage- or monocyte-conditioned medium. Urokinase type plasminogen activator production by endothelial cells and vascular smooth muscle cells was undetectable in control medium and was augmented to similar levels in response to plaque macrophage- and monocyte-conditioned media. These results demonstrate upregulation of PAI-1 production by macrophages in atheromatous plaques and the capacity of soluble products from plaque macrophages to upregulate PAI-1 production by endothelial cells and vascular smooth muscle cells in vitro. These data suggest that macrophages in atherosclerotic plaques may inhibit thrombolysis both directly and indirectly by effects of their soluble products on endothelial cells and vascular smooth muscle cells.
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PMID:Atheromatous plaque macrophages produce plasminogen activator inhibitor type-1 and stimulate its production by endothelial cells and vascular smooth muscle cells. 836 83

Human aorta was studied at early stages of atherosclerosis: intimal edema, first signs of lipoidosis, lipid spots and lipid plaques. Adhesion of Mn/Mp and lymphocytes to the aortal intima directly correlated with lipid deposits in the vascular wall. The number of mononuclear cells in the intima increased in parallel to progression of lipidosis. T-lymphocyte adhesion passed ahead of that of Mn/Mp. Cytotoxic suppressors dominated among T-lymphocytes adhered to the intima surface. Mn/Mp do not contain enzymes participating in the lipid utilization (acid lipase, acid phosphatase, nonspecific esterase) at initial stages of atherosclerosis. The activity of these enzymes starts to appear in parallel to atherosclerosis progression. HLA-DR antigen is found on the surface of T-lymphocytes and Mn/Mp indicating increased immunity of these cells.
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PMID:[Subpopulations of lymphocytes and monocytes/macrophages at the early stages of human aorta atherosclerosis]. 852 61

It is generally accepted that the foam cells in atherosclerotic lesions are derived mainly from monocytes/macrophages. We investigated whether the macrophage-derived foam cells, isolated from the atherosclerotic lesions of cholesterol-fed rabbits, would exhibit properties similar to those of blood monocytes in vitro and whether the cholesterol concentration of the macrophage-derived foam cells would decrease in the presence of an appropriate cholesterol acceptor in culture. We found that most (> 98%) of the foam cells isolated from atherosclerotic lesions were positive for anti-monocyte-macrophage antibody and nonspecific esterase. While almost all (> 98%) of the foam cells exhibited NaF-resistant, nonspecific esterase activity, the blood monocytes exhibited no such activity. Macrophage-derived foam cells contained larger amounts of cholesterol, most of it esterified, than the blood monocytes. Although blood monocytes exhibited a substantial amount of lysozyme, the freshly isolated, macrophage-derived foam cells showed no detectable lysozyme activity. The production of superoxide by macrophage-derived foam cells stimulated by PMA or opsonized zymosan was lower than that of stimulated monocytes. The cholesterol concentration of macrophage-derived foam cells decreased during five days of culture in the presence of an appropriate acceptor, such as normal and hypercholesterolemic rabbit serum and high density lipoprotein, although the rate of decrease was slow. Results suggest that macrophage-derived foam cells may be involved in both the progression and the regression of early atherosclerotic lesions.
Atherosclerosis 1997 Dec
PMID:Characteristics of macrophage-derived foam cells isolated from atherosclerotic lesions of rabbits. 943 Mar 74

Serum paraoxonase (PON1) is an esterase that is associated with high-density lipoproteins (HDLs) in the plasma; it is involved in the detoxification of organophosphate insecticides such as parathion and chlorpyrifos. PON1 may also confer protection against coronary artery disease by destroying pro-inflammatory oxidized lipids present in oxidized low-density lipoproteins (LDLs). To study the role of PON1 in vivo, we created PON1-knockout mice by gene targeting. Compared with their wild-type littermates, PON1-deficient mice were extremely sensitive to the toxic effects of chlorpyrifos oxon, the activated form of chlorpyrifos, and were more sensitive to chlorpyrifos itself. HDLs isolated from PON1-deficient mice were unable to prevent LDL oxidation in a co-cultured cell model of the artery wall, and both HDLs and LDLs isolated from PON1-knockout mice were more susceptible to oxidation by co-cultured cells than the lipoproteins from wild-type littermates. When fed on a high-fat, high-cholesterol diet, PON1-null mice were more susceptible to atherosclerosis than their wild-type littermates.
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PMID:Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. 968 59

Human serum paraoxonase (PON1) is an esterase that is bound to high-density lipoproteins (HDLs). It can hydrolyze organophosphates and its activity is inversely related to atherosclerosis. Some studies also suggest that a relationship exists between polymorphisms of the gene that encodes paraoxonase and coronary heart disease (CHD), whereas other studies, in different populations, have not found such an association. One mechanism by which certain PON1 allozymes might protect against atherosclerosis is by inhibition of the oxidation of HDL and low-density lipoprotein (LDL). Experimental studies suggest that this protection is associated with the ability of PON1 to hydrolyze specific lipid peroxides in oxidized lipoproteins. Interventions that preserve or enhance PON1 activity, as well as manipulations of PON1 polymorphisms, might help delay the onset of CHD.
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PMID:Does paraoxonase play a role in susceptibility to cardiovascular disease? 1046 49

We investigated 190 healthy, unrelated and randomly selected, north-west Indian Punjabis (M:102; F:88) for paraoxonase (PON1) polymorphism by dual substrate method and also determined lipid variables i.e., total cholesterol (TC), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL) and triglycerides (TG) in them to determine any relationship between PON1 activity, PON1 phenotypes and lipids. The basal plasma paraoxonase (PON) activity, and PON activity in presence of 1 Mol NaCl (salt activated paraoxonase i.e., SAP) were estimated by using paraoxon as substrate whereas the, phenyl acetate esterase (A) activity was estimated by using phenylacetate as substrate. Based on the ratio of SAP/A activity, three distinct phenotypes of PON1 could be determined with gene frequencies of PON*A (low activity) and PON*B (high activity) allele being 0.847 and 0.153 respectively. In the whole population on partial correlation after normalising the variables and after adjusting the lipids for age and body mass index (BMI), a significant negative correlation was observed between SAP/A ratio and TC (r = -0.290; P < 0.01) and LDL (r = -0.154; P < 0.05). However, on analysis of covariance (ANCOVA) after normalizing the lipid variables and adjusting these for age and body mass index (BMI), no significant difference could be observed in lipid profile of these three phenotypes. The lack of a significant relationship between lipids and PON1 phenotypes, suggests that PON phenotype does not significantly influence the lipid profile in north-west Indian Punjabis. However, a significant negative correlation between the PON activity and TC and LDL suggests that low PON activity could be a risk factor for atherosclerosis in these subjects.
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PMID:Paraoxonase (PON1) polymorphism & its relation with lipids in north west Indian Punjabis. 1064 1

Human serum paraoxonase (PON1) is an esterase that has been shown to decrease the susceptibility of lipoproteins to lipid peroxidation. We found a polymorphism of cytosine/thymidine (-108C/T, the number is from the ATG codon) in the upstream region of the PON1 gene. The luciferase activity was lower in the -108T allele than in the -108C allele. The serum PON1 concentrations in 132 normal subjects were as follows: -108CC>-108CT and>-108TT genotypes. The polymorphism upstream from the PON1 gene is associated with transcription of the PON1 gene and the serum PON1 concentration.
Atherosclerosis 2000 Jun
PMID:A polymorphism upstream from the human paraoxonase (PON1) gene and its association with PON1 expression. 1085 21

Human paraoxonase (PON1) is a calcium-dependent esterase closely associated with high density lipoprotein (HDL)-containing apolipoprotein AI (apoAI), which has been shown to confer antioxidant properties to HDL. PON1 has been recently implicated in the pathogenesis of atherosclerosis. Low PON1 activities have been found in familial hypercholesterolemia (FH) and diabetes mellitus. We have undertaken a study of the effect of the lipid-lowering drug simvastatin on serum PON1 activity (in relation to paraoxon and arylesterase activity), on apoAI-containing and apolipoprotein B (apoB)-containing lipoproteins, and on lipid peroxide concentrations in 64 (39 women and 25 men) unrelated FH patients. We have also analyzed the influence of the PON1-192 and PON1-55 genetic polymorphisms on the response of PON1 activity to simvastatin therapy. A venous blood sample for a baseline analysis and another after 4 months of simvastatin therapy at a dosage of 20 mg per day were taken. The major effect of simvastatin on lipid traits was to decrease serum cholesterol, low density lipoprotein (LDL) cholesterol, and lipid peroxide concentrations by 19.9%, 26.3%, and 37.3%, respectively. There was also a significant decrease in serum apoB, LDL apoB, and triglyceride concentrations (20.5%, 21.1%, and 15.6%, respectively). Conversely, simvastatin had no significant influence on very low density lipoprotein-lipid content, HDL cholesterol, apoAI concentrations, and lipoprotein AI and AI:AII particles. Remarkably, serum PON1 activity toward paraoxon significantly increased during treatment with simvastatin (168. 7+/-100.3 U/L before therapy versus 189.5+/-116.5 U/L after therapy, P:=0.005). Arylesterase activity displayed only a nonsignificant trend to increase after therapy. Whereas PON1 activity levels were significantly lower in FH patients before simvastatin therapy compared with those of 124 normolipidemic subjects (168.7+/-100.3 versus 207.6+/-125.2 U/L, respectively; P:<0.05), this difference disappeared after simvastatin therapy. After simvastatin therapy, a significantly negative correlation between PON1 activity and lipid peroxide concentration was observed (r=-0.35, P:=0.028). The latter also strongly correlated with LDL cholesterol concentration (r=0.64, P:<0.001). Serum PON1 activity levels were significantly lower in the low-activity PON1-192 QQ and PON1-55 M carriers than in R carriers and in LL carriers, respectively. No significant differences were found in the therapeutic response of PON1 activity between genotype groups (8.5% and 11.1% increase for QQ homozygous and R-carrier FH patients, respectively, and 12.7% and 9.5% increase for LL homozygotes and M carriers, respectively). We conclude that simvastatin may have important antioxidant properties through increasing serum PON1 activity, perhaps as a consequence of reducing oxidative stress, by a mechanism independent of apoAI-containing lipoprotein concentration and without the influence of PON1-192 and PON1-55 genetic polymorphisms. Further studies are clearly warranted to clarify the precise mechanism by which simvastatin therapy is associated with increased PON1 activity.
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PMID:Effect of simvastatin therapy on paraoxonase activity and related lipoproteins in familial hypercholesterolemic patients. 1097 57

An interest in the ageing process has increased greatly with increasing the population of the aged. The goal of this interest is to improve the quality of life(QOL) in the aged. In this paper, the presidential address "Ageing Society and Laboratory Medicine" at the 46th annual meeting of JSCP in Kumamoto'99 was summarized on the important research for ageing in the past decades. The paper presented was age- and gene-related changes, the latent variation of serum constituents and lipids abnormality in the ageing process. Concerning to the definition of reference value of healthy populations and the subjects who had no combined ailments, the reference interval of individuals(intra-personal), followed 5 years categorized by age, sex, and social conditions, gave a narrow range of variation than did a larger mixed populations(inter-personal). The reference intervals set would be a more sensitive reference than is the customary "normal range" for values occurring in inter-personal. Concerning to the study of the relationship between laboratory test and activity of daily living(ADL), the higher serum levels for TP, Alb, Hb, Glu, TC were observed in the higher ADL. The basic research techniques were also evaluated in the paper. The serum lipoperoxides were correlated with serum lipoprotein free radicals which caused atherosclerosis. The higher frequency of cerebral- and myocardial-infarction in the aged were observed in the higher serum LDL-C and lower serum level of arachidonic acid(AA), eicosapentaenoic acid(EPA), and AA/EPA ratio were observed in AMI patients with lower HDL-C groups than the healthy aged. Although Alzheimer(AD)'s disease had a progressive memory loss and immobile dementia and was reported the decrease of acetyltransferase activity in the brain, decrease of serum level of free choline, lyso-phosphatidylcholine, phosphatidylcholine(PC) and sphingomyelin(SM)/PC ratio were observed in spite of keeping normal serum level of SM. The decreased serum levels of pseudocholin esterase and albumin, especially mercaptoalbumin were observed in the healthy aged with advancing age. The early diagnosis and prediction of prognosis for the latent ailments in the aged was stressed. As to the study of variations of serum protein levels in the healthy aged, variations of serum proteins were classified into three types, 1) mainly acute phase reactant proteins such as alpha 1AT increased with advancing age, 2) transporting proteins such an albumin decreased and 3) proteins with no significant variation these were useful proteins for the early finding of latent ailments. The higher increase of alpha 1AT/beta 2III in the healthy aged over 60 y.o. was suspected to become severe in near future.
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PMID:[Ageing society and laboratory medicine]. 1105 92


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