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

The oxidation of low density lipoprotein (LDL) within atherosclerotic lesions may be involved in atherogenesis. LDL oxidation by cells in the presence of iron is faster at acidic pH. In addition, LDL oxidation by iron alone or iron cysteine in the absence of cells is much faster at acidic pH, even at mildly acidic pH (pH 6.5). The effect of pH on LDL oxidation by copper ions is more complex, in that acidity slows down the initial oxidation, as measured by conjugated dienes, hydroperoxides and thiobarbituric acid-reactive substances, but can increase the later stages of LDL oxidation as measured by increased macrophage uptake. Extensive LDL oxidation by cells in atherosclerotic lesions probably requires a source of iron or copper as catalysts for the oxidation. Iron in plasma is carried by the protein transferrin. Lowering the pH releases some of the iron from transferrin so that it can catalyse LDL oxidation. Copper is carried in plasma on caeruloplasmin and becomes more effective in catalysing LDL oxidation when the caeruloplasmin is preincubated at acidic pH, or even at pH 7.0. These effects can be seen with concentrations of caeruloplasmin and transferrin below those present in plasma. By analogy to other inflammatory and ischaemic sites, atherosclerotic lesions may well have an acidic extracellular pH, particularly within clusters of macrophages where the oxidative stress may also be high. This localised acidic pH may help to explain why atherosclerotic lesions are one of the few sites in the body where extensive LDL oxidation occurs.
Atherosclerosis 1997 Mar 21
PMID:Does an acidic pH explain why low density lipoprotein is oxidised in atherosclerotic lesions? 910 56

Haptoglobin is a hemoglobin-binding antioxidant showing a genetic polymorphism with three types: Hp 1-1, Hp 2-1, and Hp 2-2. The Hp 2-2 type has been associated with an increased risk of atherosclerosis. We investigated vitamin C metabolism in vivo and in vitro according to haptoglobin type in a study group of 135 healthy volunteers. Serum vitamin C concentrations were associated with haptoglobin type, showing lowest values in serum from Hp 2-2 subjects (P < 0.01). Renal threshold for L-ascorbic acid was within the normal range and metabolization to oxalate was not different among haptoglobin-type groups. Serum concentrations of other endogenous antioxidants (uric acid, bilirubin, albumin, ceruloplasmin, and total antioxidative status) were not different among haptoglobin-type groups. In vitro experiments showed a lower stability of L-ascorbic acid in blood from subjects with the Hp 2-2 type (P < 0.01). L-Ascorbic acid depletion in vitro was inversely related to haptoglobin concentration (r = -0.738). The results of this study indicate a higher rate of L-ascorbic acid oxidation in Hp 2-2 carriers because they have less protection against hemoglobin-iron driven peroxidation.
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PMID:Effect of haptoglobin on the metabolism of vitamin C. 928 Jan 80

It has been proposed that the oxidative modification of low density lipoprotein (LDL) is a key event in human atherogenesis. Copper ions can catalyse the oxidative modification of LDL in vitro and there is some evidence that they may also participate in the oxidation of LDL within the arterial wall. However, copper ions also form an intrinsic constituent of superoxide dismutase and caeruloplasmin, enzymes that may be involved in preventing oxidative injury. Atherosclerotic lesions frequently contain considerable quantities of extracellular matrix molecules. These may contribute to the expansion of the arterial neointima, causing luminal narrowing. They may also play a beneficial role by stabilising the plaque. Copper is an essential component of lysyl oxidase, an enzyme involved in the biosynthesis of collagen, which is a major constituent of the extracellular matrix. The impact of alterations in body copper status on atherogenesis is therefore difficult to predict. Experimental and epidemiological data are conflicting and therefore do not provide a clear resolution of this issue. We have reviewed the biochemical and cellular effects of copper ions that may play a role in atherogenesis.
Atherosclerosis 1997 Sep
PMID:The possible role of copper ions in atherogenesis: the Blue Janus. 962 90

There has been considerable debate about how copper status may affect the biochemical and cellular processes associated with atherogenesis. In the present study we have attempted to address this issue directly by investigating the effects of dietary copper supplementation on processes likely to contribute to atherogenesis, using the cholesterol-fed New Zealand White rabbit model. Age matched rabbits (n = 16) were fed a 0.25-1% cholesterol diet to maintain plasma cholesterol concentrations at approximately 30 mmol/l. Eight of these animals also received 0.2% copper acetate. Control animals (n = 8) received rabbit chow without supplements. After 13 weeks on the experimental diets the animals were killed. Integrated cholesterol levels were similar for the cholesterol-fed animals (31.1+/-2.5 vs. 29.9+/-1.9 mmol/l weeks; P>0.05). Although integrated plasma copper levels were higher in the animals receiving the copper supplements, these did not differ significantly (19.0+/-4.8 vs. 15.1+/-2.9 micromol/l weeks; P>0.05). Tissue concentrations of copper were higher in the copper fed animals compared to those on cholesterol alone in aortic 14.0+/-0.75 vs. 1.8+/-0.2 microg/g wet tissue; P<0.05), carotid artery (11.4+/-3.5 vs. 4.9+/-0.9 microg/g wet tissue; P<0.05), and hepatic (332.5+/-28.6 vs. 3.3+/-1.1 microg/g wet tissue; P<0.0001) samples. The concentration of copper within the carotid artery was also significantly higher than that within the aorta (7.5+/-1.8 vs. 2.4+/-0.4 microg/g wet tissue; P<0.05). In animals fed a normal rabbit chow aortic, carotid and hepatic copper concentrations were 3.7+/-0.8, 9.4+/-3.4, and 5.0+/-1.6 microg/g, respectively. These values did not differ significantly from the cholesterol-fed animals (P>0.05). Plasma concentrations of caeruloplasmin, the major copper carrying protein, were estimated as plasma ferroxidase activity and were similar for the groups (P>0.05), as were aortic superoxide dismutase activity levels (P>0.05). Copper supplementation was associated with increased mononuclear cell adhesion to the endothelium of the carotid endothelium, with 2.6+/-0.3 adherent monocytes/1000 endothelial cells in the cholesterol plus copper-fed animals compared to 1.3+/-0.3 in the cholesterol-fed group (P = 0.0006), and 0.1+/-0.1 in the control animals (P<0.002). This may reflect the higher concentrations of copper found within the carotid artery. Histology of the thoracic aorta at the level of the third and sixth intercostal arteries, showed that copper supplementation was associated with significantly smaller intimal lesions (P<0.05 and P<0.01, respectively). These data suggest that copper supplements possibly inhibit the progression of atherogenesis.
Atherosclerosis 1999 Sep
PMID:Dietary copper supplementation reduces atherosclerosis in the cholesterol-fed rabbit. 1048 84

A total of 1200 patients with angina were cardiac catheterized establishing that 63% had 70-100% stenosis, 12% had 10-69% stenosis of one or more of their coronary arteries and 25% had microvascular angina listed as 0% stenosis. Prior to catheterization 10 ml of blood was drawn and the plasma subjected to analysis for the concentration of cholesterol, lipid peroxides (LPX), total antioxidant capacity (TAOC), fibrinogen (FB), ceruloplasmin (CP) and activation of polymorphonuclear leukocytes (PMNLs). Comparisons were made to non-smoking controls without angina. Significant differences in LPX were found between the patients with 0 and 10-69% stenosis (P<0.001), with 10-69 and 70-100% stenosis (P<0.001), and with 0 and 70-100% stenosis (P<0.001). Under 70 years of age there was a significant difference in LPX between patients with all levels of stenosis and age and sex matched controls (P<0.001). Differences in the mean plasma cholesterol concentration for different levels in the degree of stenosis were not significant, indicating that LPX provided consistent data on the severity of stenosis while the plasma cholesterol concentration did not. Compared with controls an increase in activation of PMNLs (P<0.01), an increase in concentration of both FB and CP (P<0.01) and a decrease in total antioxidant capacity were noted in the plasma of catheterized patients. In summary the concentration of oxidation products rather than the concentration of cholesterol in the plasma identified stenosis in cardiac catheterized patients.
Atherosclerosis 2000 Mar
PMID:The relationship of oxidized lipids to coronary artery stenosis. 1070 30

The relationships among concentrations of copper and zinc, the oxidase activity of ceruloplasmin (Cp) in serum, and Cu,Zn-SOD (superoxide dismutase) activity in erythrocytes were investigated in men with atherosclerosis obliterans (AO) and a control group. The oxidase activity of Cp was measured with o-dianisidine dihydrochloride as a substrate, and Cu,Zn-SOD activity in erythrocytes by using the RANSOD kit. The lipid profile and uric acid concentration were determined in AO and control groups. The results showed higher copper and zinc concentrations in serum in the AO group (20.0+/-3.5 and 18.0+/-3.2 micromol/L, respectively) in comparison with the control group (15.6+/-2.3 and 14.7+/-1.9 micromol/L). The Cp activity in serum was higher in the AO group (174.2+/-61.8 U/L) than in the control group (93.7+/-33.9 U/L), and a significant difference was found in the activity of Cu,Zn-SOD in erythrocytes (2389+/-1396 and 1245+/-365 U/g Hb, respectively) between both groups. The activity of Cu,Zn-SOD was positively correlated with copper in the control group (r=0.73), but not in AO, and negatively with uric acid concentration (r= -0.63) in the AO group. The oxidase activity of Cp was correlated with copper, but not zinc, in AO and control groups (r> or =0.65). Negative correlation coefficients were calculated for uric acid and copper and zinc concentrations in the AO group (-r > or = 0.61). Increased copper concentrations and oxidase activity of Cp in serum in AO and the activity of Cu,Zn-SOD in erythrocytes could result from atherosclerotic disease, accompanied by chronic ischemia of a lower limb. These results suggest also that relationship between copper concentration and Cu,Zn-SOD activity in erythrocytes found in the serum of healthy subjects may be disturbed in pathologic conditions.
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PMID:Copper and zinc concentrations and the activities of ceruloplasmin and superoxide dismutase in atherosclerosis obliterans. 1094 69

The metabolism of apolipoprotein (apo) A-IV in diabetes mellitus (DM) is poorly understood. Several factors, such as dietary fat intake, fat malabsorption, acute inflammation, and hormonal dysregulation can disturb the plasma apo A-IV concentration. We have compared the plasma apo A-IV concentrations in patients with type 1 DM and DM secondary to chronic pancreatitis to determine the effects of combinations of these factors. We examined 4 groups of male patients with chronic pancreatitis without diabetes (ND-CP) (n = 12), diabetes secondary to chronic pancreatitis and insulin-treated (CP-DM) (n = 32), type 1 diabetes (n = 25), and controls (n = 20). Plasma apo A-IV was significantly lower in the chronic pancreatitis patients (ND-CP and CP-DM) than in the other patients. Inflammatory proteins (fibrinogen, ceruloplasmin, and haptoglobin) were significantly elevated in the 2 chronic pancreatitis groups. The apo A-IV concentration was positively correlated with hemoglobin A(1c) (HbA(1c)) percentage in each group of diabetic patients (CP-DM, r =.35; P =.046; type 1 DM, r =.53; P =.010), in both groups of diabetic patients (r =.472; P <.0001) and negatively correlated with ceruloplasmin concentration in each group of diabetic patients (CP-DM, r = -.48; P =.0052; type 1 DM, r = -.66; P =.003), in both groups of diabetic patients (r = -.561; P <.0001), and in the whole population (r = -.463; P <.0001). Apo A-IV was also negatively correlated with haptoglobin in type 1 DM patients (r = -.434; P =.0435), in the both groups of diabetic patients (r = -.349; P =.0154), and in the whole population (r = -.351; P =.0019). Multiple linear regression analysis revealed that only HbA(1c) and ceruloplasmin were independent explanatory variables. Plasma apo A-IV is positively correlated with HbA(1c) suggesting that hyperglycemia per se selectively affects apo A-IV metabolism. The correlation between the concentrations of inflammatory protein and apo A-IV suggest a link between chronic inflammation and apo A-IV synthesis or catabolism. As apo A-IV is involved in reverse cholesterol transport, its low level in CP-DM may contribute to the accelerated development of atherosclerosis in these patients.
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PMID:Effect of the inflammation, chronic hyperglycemia, or malabsorption on the apolipoprotein A-IV concentration in type 1 diabetes mellitus and in diabetes secondary to chronic pancreatitis. 1155 32

Insulin resistance syndrome (IRS) is a cluster of prevalent conditions including glucose intolerance, hypertension and dyslipidemia, which commonly predispose to cardiovascular disease. However, the mechanism by which IRS is related with cardiovascular disease is not yet settled. Recently, it has been hypothesized that atherosclerosis is an inflammatory disease and that an increase in oxidative stress plays a key role in causing endothelial dysfunction associated with atherosclerosis. There has been, however, no study directly relating IRS with oxidative stress in human subjects. We measured various markers of oxidative stress among subjects who participated in a population-based epidemiological study performed in 1996. IRS was defined as non-diabetic subjects having more than two of three salient features of the syndrome (glucose intolerance, hypertriglyceridemia/low high density lipoprotein (HDL)-cholesterol and hypertension). The subjects with IRS (n=70) showed higher plasma malondialdehyde (MDA; 2.10+/-1.43 vs. 1.63+/-1.21 micromol/ml, P=0.009), homocysteine (16.32+/-8.34 vs. 13.06+/-6.49 micromol/l, P=0.002) and ceruloplasmin concentrations (29.80+/-5.28 vs. 27.39+/-5.10 mg/dl, P=0.002) than control subjects (n=196). Plasma MDA concentration was positively correlated with waist-to-hip ratio (r=0.124, P=0.044), and with plasma triglyceride (TG; r=0.163, P=0.008), ferritin (r=0.200, P=0.002) and homocysteine concentrations (r=0.136, P=0.032). These results suggest that increase in oxidative stress may contribute to the development of cardiovascular disease in IRS.
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PMID:Oxidative stress markers in Korean subjects with insulin resistance syndrome. 1173 6

Epidemiological studies have implicated periodontal disease (PD) as a risk factor for the development of cardiovascular disease (CVD). These studies addressed the premise that local infection may perturb the levels of systemic inflammatory mediators, thereby promoting mechanisms of atherosclerosis. Levels of inflammatory mediators in the sera of subjects with only PD, only CVD, both diseases, or neither condition were compared. Subjects were assessed for levels of C-reactive protein (CRP), serum amyloid A (SAA), ceruloplasmin, alpha(1)-acid-glycoprotein (AAG), alpha(1)-antichymotrypsin (ACT), and the soluble cellular adhesion molecules sICAM-1 and sVCAM by enzyme-linked immunoabsorbent and/or radial immunodiffusion assays. CRP levels in subjects with either condition alone were elevated twofold above subjects with neither disease, whereas a threefold increase was noted in subjects with both diseases (P = 0.0389). Statistically significant increases in SAA and ACT were noted in subjects with both conditions compared to those with one or neither condition (P = 0.0162 and 0.0408, respectively). Ceruloplasmin levels were increased in subjects with only CVD (P = 0.0001). Increases in sVCAM levels were noted in all subjects with CVD (P = 0.0054). No differences in sICAM levels were noted among subject groups. A trend toward higher levels of AAG was noted in subjects with both conditions and for ACT in subjects with only PD. Immunohistochemical examination of endarterectomy specimens of carotid arteries from subjects with atherosclerosis documented SAA and CRP deposition in association with atheromatous lesions. The data support the hypothesis that localized persistent infection may influence systemic levels of inflammatory mediators. Changes in inflammatory mediator levels potentially impact inflammation-associated atherosclerotic processes.
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PMID:Systemic inflammation in cardiovascular and periodontal disease: comparative study. 1187 89

Serum ceruloplasmin, C3 complement and albumin in 119 male smokers and 65 male non-smoker; from a military unit in Bangkok were investigated in this study. The serum ceruloplasmin concentration was found to be significantly higher in smokers than in non-smokers. However, the serum albumin concentration in smokers was statistically significantly lower than in non-smokers. Significant associations were also found between ages, albumin levels and the quantity of cigarettes smoked. There was a significant positive correlation between serum ceruloplasmin and C3 complement concentrations. An association between the quantity of cigarettes smoked and albumin was also found, as well as a significant relationship between smoking and the quantities of cigarettes smoked to serum ceruloplasmin levels when smoking and the quantity of cigarettes smoked were taken as independent variables, and the serum ceruloplasmin levels as a dependent variable. This might suggest that high concentrations of the acute-phase protein, i.e. ceruloplasmin, might constitute a risk of developing atherosclerosis or cardiovascular disease in smokers.
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PMID:The effect of cigarette smoking on ceruloplasmin and C3 complement: risk of cardiovascular disease (atherosclerosis). 1212 14


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