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)

Diabetes mellitus (DM) is a common disease affecting over 124 million individuals worldwide. DM is associated with high risk of atherosclerosis and renal, neural, and ocular damage. Increased oxidant stress has been implicated in the pathogenesis of DM. An increase in serum ceruloplasmin (Cp) levels has also been reported in Type 2 DM. Cp permits the incorporation of iron into transferrin (Trf). Trf inhibits iron ion-dependent OHo formation from H2O2. Patients with diabetes have increased levels of plasma lipid peroxidation products. In this study, we evaluated 50 patients with Type 2 DM and 21 clinically healthy subjects. Patients were divided into two groups. Group I included 29 patients without diabetic complications, Group II 21 with diabetic complications. Serum Cp, Trf, C-reactive protein (CRP), triglyceride (TG), cholesterol (Chol), and malondialdehyde (MDA) levels are studied. Serum Cp, CRP, TG, Chol, and MDA levels in diabetic patients were significantly higher than those of controls. Trf levels were significantly lower in diabetic patients than those of the controls. Cp, CRP, HbA1C, and MDA levels in Group II were significantly higher than those of Group I. Our results indicate that oxygen free radicals are formed in DM and can result in diabetic complications and that a prooxidant/oxidant imbalance is involved in the tissue injury in DM and diabetic complications.
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PMID:Levels of ceruloplasmin, transferrin, and lipid peroxidation in the serum of patients with Type 2 diabetes mellitus. 1520 35

It has previously been shown that dietary copper can modulate the extent of atherosclerosis in the thoracic aorta of cholesterol-fed rabbits. The metabolism of copper and zinc are closely related, and it has been hypothesized that the balance of dietary copper to zinc may be important in determining coronary risk. Hence, we have investigated the interaction between dietary copper and zinc in atherogenesis in the New Zealand White rabbit. Juvenile male rabbits were randomly allocated to eight groups. Four groups were fed a normal chow diet with zinc (0.5%, w/w), copper (0.2%, w/w), copper plus zinc or neither in their drinking water for 12 weeks. Four other groups were fed a diet containing 0.25-1% (w/w) cholesterol plus zinc, copper, both or neither. Serum cholesterol of individual animals was maintained at approximately 20 mmol/l. Integrated plasma cholesterol levels were similar for all groups receiving cholesterol and significantly higher than those in the chow-fed groups (P < 0.001). Aortic copper concentrations were higher in the animals receiving cholesterol diets with copper compared to rabbits receiving normal chow and copper (P < 0.001). Aortic zinc content was significantly higher in cholesterol-fed rabbits supplemented with zinc alone or with copper than in those fed cholesterol alone (P < 0.001). Plasma ceruloplasmin concentrations were significantly higher in groups receiving cholesterol, irrespective of their trace element supplementation (P < 0.001). However, trace element supplementation increased the level significantly (P < 0.05). Trace element supplements did not appear to affect erythrocyte superoxide dismutase in the cholesterol-fed animals; however, zinc supplementation was associated with a significant increase in the enzyme in chow-fed animals (P < 0.05). The activity of the enzyme per mg of protein in aortic tissue was higher in animals receiving copper in the presence of cholesterol (P < 0.05) but not significantly so in its absence. Dietary trace element supplementation in cholesterol-fed animals was associated with a significant reduction in aortic lesion area. Plasma thiobarbituric acid-reactive substances and FOX concentrations were both significantly higher in the cholesterol-fed rabbits compared with the animals that fed on a chow diet (P < 0.001), and these were reduced significantly by dietary copper or zinc supplementation (P < 0.001). Hence, dietary supplements of copper or zinc at the doses used both inhibited aortic atherogenesis in the cholesterol-fed rabbits, although there was no significant additional effect when given in combination.
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PMID:The effects of coadministration of dietary copper and zinc supplements on atherosclerosis, antioxidant enzymes and indices of lipid peroxidation in the cholesterol-fed rabbit. 1537 59

The diabetes mellitus occurs as an important disease at elderly people, to whom the micro- and macrovascular complications represent a major cause of morbidity and mortality. Experimental researches of the last years proved that the oxidative stress may be the common mechanisms that intervenes in the occurrence of the diabetes complications as well as in the aging process and is responsible for the increased prevalence of chronic complications at elderly diabetics. Starting from this information, we performed a comparative study where we followed the intensity of the oxidative stress at elderly diabetics as compared to adult diabetics and non-diabetic elderly people. At the same time, we have followed the involvement of oxidative stress in the occurrence of diabetic microangiopathy and atherosclerosis. 155 patients from the 4th Medical Clinic were studied during 2000-2003. These patients were divided into three lots: lot 1: elderly diabetics, lot 2: adult diabetics, lot 3: elderly non-diabetics. At these patients we have followed comparatively the intensity of the oxidant status by determining the plasma malondialdehyde (MDA) and the anti-oxidant status by determining the plasma ceruloplasmin, as well as the correlations of these two parameters with the chronic complications of diabetes. At elderly diabetics there is an increased oxidative stress underlined by an increased plasma level of MDA and ceruloplasmin as compared to the adult diabetics and non-diabetic elderly people and this increased oxidative stress is involved in the development of the chronic complications at this patients. In case of elderly diabetics, the age and the illness may induce the formation of oxygen-derived free radicals with synergic effect in injuring tissues and organs.
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PMID:The oxidative stress in the development of diabetes chronic complications in the elderly. 1552 29

Although ceruloplasmin (CP), a copper containing metalloenzyme, possesses antioxidant properties (e.g. ferroxidase activity), elevated circulating CP is associated with cardiovascular disease (CVD). This ambivalence is possibly due to the capacity of CP, via its coppers, to promote vasculopathic effects that include lipid oxidation, negation of nitric oxide bioactivity and endothelial cell apoptosis. In turn, these effects that are mediated by increased formation of reactive oxygen species (ROS), such as superoxide and hydrogen peroxide. There is also evidence that risk factors for CVD (in particular, diabetes mellitus and hyperhomocysteinaemia) may augment the vasculopathic impact of CP. In turn, it appears that ROS disrupt copper binding to CP, thereby impairing its normal protective function while liberating copper which in turn may promote oxidative pathology. The objective of this review, therefore, is to consider the epidemiology and pathophysiology of CP in relation to CVD, with particular emphasis on the relationship between CP and oxidative stress.
Atherosclerosis 2006 Aug
PMID:Does oxidative stress change ceruloplasmin from a protective to a vasculopathic factor? 1641 46

The role of sialic acid (SA) in the pathogenesis of atherosclerosis and as a predictor of cardiovascular events has attracted much attention in recent years. However, most studies investigating the role of total and lipid-bound sialic acids (TSA and LSA) in the pathogenesis of atherosclerosis lack information on the reason for the elevated SA concentrations in coronary heart disease and myocardial infarction. Since the inflammation-sensitive proteins are glycoproteins with SA residues, an increase in their levels due to some type of acute-phase reaction or inflammation could be responsible for the elevated TSA levels in acute myocardial infarction (AMI). Elevated serum SA levels might also be due to either shedding or secretion of free SA from the cell or cell membrane surface if neuraminidase levels are increased, or to the release of cellular SA-containing glycolipids and/or glycoproteins into plasma from myocardial cells after AMI. The aim of the present study was to investigate both the possible role of SA-rich inflammation-sensitive proteins and the cell damage due to elevated serum TSA levels in AMI. A possible role of serum LSA as an indicator of the shedding or secretion of SA from the cell or cell membrane surface in AMI was also evaluated. The study included 38 subjects with AMI and 32 healthy volunteers. Serum TSA and LSA were determined using the methods of Warren and Katopodis, respectively. The concentrations of serum SA-rich inflammation-sensitive proteins, namely alpha1-antitrypsin, alpha2-macroglobulin and ceruloplasmin were determined immunoturbidimetrically. Our data showed that: a) mean levels of serum TSA and LSA and SA-rich inflammation-sensitive proteins in patients with AMI were significantly increased; and b) there was a significant positive correlation between TSA and LSA and alpha1-antitrypsin in patients with AMI. Since the transfer of free SA to lipoproteins is required for an increase in serum LSA levels, and free SA for this transfer can be provided by the secretion of SA from the cell, it is obvious that the shedding or secretion of SA from the cell membrane surface or release of cellular SA from cells into the bloodstream due to cell damage after AMI also occur after AMI. As a result, we can report that either the shedding or secretion of SA from the cell or cell membrane surface and the increased output of SA-rich inflammation-sensitive proteins may together be responsible for the elevated TSA levels in AMI.
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PMID:Relationship between serum sialic acids, sialic acid-rich inflammation-sensitive proteins and cell damage in patients with acute myocardial infarction. 1647 8

It was reported that lipid peroxidation (LPO) products increase in rheumatoid arthritis (RA) patients and increased LPO products reduce many antioxidants. Lipid hydroperoxides (LOOHs) are byproduct of LPO. Paraoxonase (PON), arylesterase (ARE), free sulfhydryl (SH) groups, and ceruloplasmin (CP) are enzymes or proteins with antioxidant characteristics. This study aims to determine the levels of LOOHs and SH, and the activities of PON1, ARE, and CP in RA patients. The study included 47 active RA cases and 23 healthy volunteers. The levels of LOOHs and SH, and the activities of PON1, ARE, and CP were determined using appropriate methods. Student's t test and Spearman's correlation analysis methods were employed in the statistical evaluation. The level of LOOHs was found to be higher (p<0.001), while the level of SH and the activities of PON1, ARE, and CP were found to be lower (p<0.001, <0.001, <0.01, and <0.01, respectively) in the RA patient group when compared with the control group. There was a negative correlation between the level of LOOHs and the activity of PON1 in the patient group (r= -0.420 and p<0.01). The results of our study indicate increased oxidant and decreased antioxidant presence in RA patients. PON1 and ARE are known to have antiatherosclerotic effects in addition to their antioxidant characteristics. As the decrease in these antioxidants, resulting from increased oxidative stress in RA patients, development of atherosclerosis besides tissue injury seems inevitable.
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PMID:Paraoxonase and arylesterase levels in rheumatoid arthritis. 1664 6

Prospective studies have demonstrated that an imbalance between oxidative damage and antioxidative protection can play a role in the development and progression of atherosclerosis. Also, genotypes with the apolipoprotein E epsilon4 allele have been associated with an increase risk for this pathology. Based on this knowledge, the aim of this study was to evaluate indicators of the redox balance, trace elements, and apolipoprotein E allelic profile in subjects from the Lisbon population with clinically stable atherosclerosis, at risk for atherosclerotic events, and in healthy subjects for comparison. The activities of superoxide dismutase in erythrocytes and glutathione peroxidase in whole blood, plasma total thiols, and serum ceruloplasmin were kept unchanged among the three groups. Serum alpha- tocopherol was increased in atherosclerotic patients. Total malondialdehyde in serum and protein carbonyls in plasma, which are indicators of lipid and protein oxidative damage, respectively, reached their highest values in risk subjects. The concentrations of potassium and calcium, in plasma and in blood cells, were slightly elevated in patients and might reflect an electrolytic imbalance. Regarding the apolipoprotein E polymorphism, atherosclerotic patients had an increased incidence of the high-risk genotypes for atherogenesis (epsilon3/epsilon4 and epsilon4/epsilon4). A multivariate model applied to the general population using most of the parameters clearly separated the three groups at study (i.e., the healthy group from the steady-state group of risk disease and from the atherosclerotic one). As shown by us, the usefulness of biochemical and complementary genetic markers is warranted for a better knowledge on atherosclerosis molecular basis.
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PMID:Systemic markers of the redox balance and apolipoprotein E polymorphism in atherosclerosis: the relevance for an integrated study. 1694 16

Oxidative stress and oxidative damage to tissues are common end points of chronic diseases such as atherosclerosis, diabetes, and rheumatoid arthritis. Oxidative stress in diabetes coexists with a reduction in the antioxidant status, which can further increase the deleterious effects of free radicals. The aim of the present study was to evaluate the possible protective effects of Murraya koenigii leaves extract against beta-cell damage and antioxidant defense systems of plasma and pancreas in streptozotocin induced diabetes in rats. The levels of glucose and glycosylated hemoglobin in blood and insulin, Vitamin C, Vitamin E, ceruloplasmin, reduced glutathione and TBARS were estimated in plasma of control and experimental groups of rats. To assess the changes in the cellular antioxidant defense system such as the level of reduced glutathione and activities of superoxide dismutase, catalase and glutathione peroxidase were assayed in pancreatic tissue homogenate. The levels of glucose, glycosylated hemoglobin, insulin, TBARS, enzymatic and non-enzymatic antioxidants were altered in diabetic rats. These alterations were reverted back to near control levels after the treatment of M. koenigii leaves extract. Transmission electron microscopic studies also revealed the protective nature of M. koenigii leaves on pancreatic beta-cells. These findings suggest that M. koenigii treatment exerts a therapeutic protective nature in diabetes by decreasing oxidative stress and pancreatic beta-cell damage. The antioxidant effect of the M. koenigii extract was compared with glibenclamide, a well-known hypoglycemic drug.
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PMID:Beneficial effects of Murraya koenigii leaves on antioxidant defense system and ultra structural changes of pancreatic beta-cells in experimental diabetes in rats. 1718 70

Investigation of the mechanisms of atherosclerosis has determined that inflammation plays a central role in the development, progression, and outcome of acute coronary syndrome (ACS). C-reactive protein (CRP) plasma levels increase in patients with ACS. CPR is an important prognostic marker in ACS, following angioplasty, and in the long-term management of post-infarction patients. Although CRP will remain over time a useful marker, the role and implications of increased plasma concentrations of other acute phase proteins (APPs), such as alpha-1-antitrypsin (A1AT), alpha-1 glycoprotein (A1GP), haptoglobin (HG), ceruloplasmin (CP), and C3c and C4 complement fraction, in patients with ACS are still not completely defined. This short review summarizes the experimental and clinical evidence regarding the role, and the biological and clinical significance of these other APPs in ACS.
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PMID:Acute phase proteins in atherosclerosis (acute coronary syndrome). 1885 39

Vascular calcification plays a role in the pathogenesis of atherosclerosis, diabetes, and chronic kidney disease. Human aortic smooth muscle cells (HSMCs) undergo mineralization in response to elevated levels of inorganic phosphate (Pi) in an active and well-regulated process. This process involves increased activity of alkaline phosphatase and increased expression of core binding factor alpha-1, a bone-specific transcription factor, with the subsequent induction of osteocalcin. Mounting evidence suggests an essential role for the heme oxygenase 1 (HO-1)/ferritin system to maintain homeostasis of vascular function. We examined whether induction of HO-1 and ferritin alters mineralization of HSMCs provoked by high Pi. Upregulation of the HO-1/ferritin system inhibited HSMC calcification and osteoblastic differentiation. Of the products of the system, only ferritin and, to a lesser extent, biliverdin were responsible for the inhibition. Ferritin heavy chain and ceruloplasmin, which both possess ferroxidase activity, inhibited calcification; a site-directed mutant of ferritin heavy chain, which lacked ferroxidase activity, failed to inhibit calcification. In addition, osteoblastic transformation of HSMCs provoked by elevated Pi (assessed by upregulation of core binding factor alpha-1, osteocalcin, and alkaline phosphatase activity) was diminished by ferritin/ferroxidase activity. We conclude that induction of the HO-1/ferritin system prevents Pi-mediated calcification and osteoblastic differentiation of human smooth muscle cells mainly via the ferroxidase activity of ferritin.
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PMID:Ferritin prevents calcification and osteoblastic differentiation of vascular smooth muscle cells. 1942 91


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