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)

Cardiovascular complications in renal replacement therapy remain prevalent today. The question, "Is atherosclerosis accelerated in peritoneal dialysis (PD) patients," has not been resolved. Many cross-sectional studies have revealed that there are more atherogenic lipid profiles in continuous ambulatory peritoneal dialysis (CAPD) than in other dialytic modalities. However, it is not certain that CAPD per se may contribute to lipid abnormalities in continuing PD for a long time. Therefore, we tried to assess whether CAPD itself may change lipid profiles in the long-term period on CAPD. We measured conventional lipid profiles in 16 stable CAPD patients in whom total cholesterol (T.chol.) levels remained under 240 mg/dL at the time of starting observation. Diabetic end-stage renal disease (DMESRD) patients were excluded from this study. Blood sampling was performed under strict conditions indicating overnight fasting with 10 hours dwell of 2 L of 1.5% Dianeal. Plasma levels of T.chol., triglyceride, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and atherogenic lipoprotein (apo B/A-I) did not show significant changes by serial measurements from the sixth month to the thirtieth month following the commencement of CAPD as their initial dialysis treatment. Recently it is reported that high plasma levels of Lp(a) lipoprotein are an independent risk factor in cardiovascular events in renal replacement therapy because Lp(a) has a close relation to intravascular thrombosis and acceleration of atherosclerosis. We found that the incident of vascular accidents was five episodes among 33 patients with higher (> 31 mg/dL) Lp(a) levels, while there was only one episode in 45 patients with lower (< 30 mg/dL) Lp(a) levels (p < 0.05, odds ratio: 7.9). However, severity of aortic calcification and incidence of positive treadmill test showed no difference in these two groups. No significant correlation was observed between duration on CAPD and plasma Lp(a) levels. From the fact mentioned above, we speculate that CAPD does not essentially affect lipid profiles if determined under the strict condition of blood sampling. In order to evaluate the atherosclerosis noninvasively, we have measured aortic pulse wave velocity (AoPWV) in 33 stable CAPD patients excluding those with DMESRD by two years' interval. Fifteen cases (46%) increased in AoPWV, however, lipid profiles did not differ from those of nonadvanced patients. Calcification of arteries is further evidence of acceleration in atherosclerotic change. Therefore, we have graded severity of abdominal aortic calcification into three categories: grade I denoted nil calcification, grade II denoted patchy calcification, and grade III denoted calcification along the entire abdominal wall, having a lead-pipe shape by lateral view of plain abdominal x-ray film. There were significant differences in the duration of CAPD (grade I: 41 months, grade II: 60 months, grade III: 68 months). AoPWV showed least in the grade I group, faster in grade II, and fastest in grade III, while lipid profiles did not show significant differences in three categories. From the analysis of serial changes of lipid profiles, AoPWV and aortic calcification, CAPD may present some risk of accelerating atherosclerosis, at least in some patients on long-term treatment. Risk factors contributing to acceleration of atherosclerosis is result not from lipid abnormalities, but from other factors which remained to be seen, for example, abnormalities in calcium metabolism.
Perit Dial Int 1996
PMID:Is atherosclerosis accelerated by CAPD? 872 97

It has been shown that serum total homocysteine (HC) is a risk factor for vascular disease which characterizes endothelial damage. The incidence of vascular disease is increased in continuous ambulatory peritoneal dialysis (CAPD) patients. Our aim was to investigate: (1) whether concentration of HC correlates with atherosclerotic and inflammatory events, and (2) if fish oil therapy can retard the disturbance in lipid metabolism which promotes atherosclerosis. Fourteen patients with various degrees of impaired peritoneal clearance and lipid metabolism were observed. In all patients the serum HC was elevated. Seven patients were treated with fish oil for three months. The results indicate an average increase of HC (+18%), total cholesterol (+6.6%), aggregation of erythrocytes (+9%), and an average decrease of dialysate-to-plasma creatinine (D/P) ratio (-7%), deformability of erythrocytes (-8%), and normalization of elevated soluble interleukin-2 receptor (sIL-2R) values. Regression analysis of all data demonstrated a significant correlation between HC and parameters of lipid metabolism and hemorheology. There were no significant correlations between HC and peritoneal function and serum cytokine levels. We conclude that the treatment in CAPD patients with fish oil did not improve the lipid metabolism disturbances in atherosclerosis and peritoneal function. Elevated HC confirms the progression of the disease.
Perit Dial Int 1996
PMID:Increased serum level of total homocysteine in CAPD patients despite fish oil therapy. 872 1

Prostaglandins, thromboxanes, and other eicosanoids represent a widespread lipid-mediator system for intercellular signalling, and, hence, have multiple cellular actions. Thus it is not surprising that numerous events in the pathogenesis of atherosclerosis are associated with an altered formation of eicosanoids. To reconsider the availability of eiconsanoid precursors as one possible cause of atherogenesis, the dietary intake and the serum concentrations of arachidonic acid (AA) and eicosapentaenoic acid (EPA) were determined in patients with high risk for atherosclerosis on continuous ambulatory peritoneal dialysis (CAPD) with and without diabetes in comparison to healthy controls and diabetic patients without late complications. The factor AA/EPA in serum was created as a marker for the atherosclerosis risk. The setting was in a CAPD unit in one city hospital. There were 26 CAPD patients [9 with insulin-dependent diabetes mellitus (IDDM), 9 with noninsulin-dependent diabetes mellitus (NIDDM), and 8 without diabetes], 27 IDDM without late complications, and 41 healthy control persons. The AA levels in serum were significantly higher in all of the CAPD groups. In contrast, the EPA concentrations in serum were significantly lower in the CAPD groups, with the lowest EPA levels found in the CAPD-IDDM group. Therefore, the factors AA/EPA in serum were significantly higher in all of the CAPD groups, and again significantly higher in the CAPD-IDDM group than in the other CAPD groups. No differences in the amount of dietary intake of AA existed between the groups. The daily intake of EPA was significantly highest in the control group. Higher concentrations of AA and a lack of n-3 fatty acids lead in the presence of a reduced prostaglandin I2 biosynthesis, to a higher formation rate of potentially proatherogenic metabolites such as thromboxane A2, a vasoconstricting and platelet aggregating agent. Thus, the quotient AA/EPA could possibly be used as a marker of atherogenicity in the future.
Perit Dial Int 1996
PMID:Eicosanoid precursors: potential factors for atherogenesis in diabetic CAPD patients? 872 2

A major cause of the morbidity and mortality of patients with end-stage renal disease (ESRD) is related to disorders of large blood vessels, especially coronary heart disease. Atherosclerosis, the most common form of this disease, is known to result from abnormalities in plasma lipoproteins, as well as from factors that damage the vessel wall. Two well-known risk factors for coronary heart disease are elevated plasma concentrations of LDL and reduced concentrations of HDL. This latter disorder is often accompanied by elevated triglycerides. Low HDL and elevated triglycerides are commonly associated with ESRD. Dialysis with high flux membranes differs from conventional dialysis in a number of ways. These include better biocompatibility and increased flux of larger molecules. Although several previous studies had suggested that dialysis with high flux membranes improves plasma lipoprotein profiles, a definitive cross-over designed study to assess the roles of high flux versus biocompatibility in altering lipoprotein profiles had not been done. Preliminary data from such a study are presented. These data confirm the beneficial effects of high flux membranes to reduce plasma triglycerides and suggest that this effect is primarily due to the high flux, and not the biocompatible, feature of the membranes.
Nephrol Dial Transplant 1996
PMID:High flux dialysis membranes improve plasma lipoprotein profiles in patients with end-stage renal disease. 880 7

Uraemic patients suffer from haemorrhagic disorders and accelerated atherosclerosis. To evaluate the possible role of the vessel wall in these haemostatic alterations associated with uraemia, we investigated the effect of a uraemic milieu on human endothelial cell (EC) cultures and the reactivity of the extracellular matrices (ECM) generated by these cells towards platelets. EC cultures were exposed to a pool of sera (20% in the culture medium) obtained either from uraemic patients or from normal donors, and the following parameters were evaluated: (1) EC viability (trypan blue exclusion test); (2) von Willebrand factor (vWF) levels in supernatants and associated with ECM; (3) the reactivity of EC and EC-derived ECM towards platelets, measured 'ex vivo' under flow conditions (5 min, wall shear rate 800 s-1); and (4) ultrastructure of the ECM. The viability of EC cultured in the presence of uraemic sera was similar to controls. Platelet interaction with ECM generated by EC exposed to uraemic sera was significantly reduced (P < 0.05). This decrease was mainly related to a reduction in platelet adhesion (9.8 +/- 1.9% vs 16.7 +/- 1.8% in controls, P < 0.02). VWF levels in supernatants and associated with ECM were similar to controls. Ultrastructural analysis of the ECM generated by EC exposed to uraemic sera revealed a deficient matrix. An increased removal of EC was observed in experiments in which EC cultured in the presence of uraemic sera were perfused with citrated blood. These results indicate that a uraemic milieu induces quantitative and qualitative changes in the vascular subendothelium, characterized by a less intrincate network of fibrils, as well as a decreased attachment of EC and reduced thrombogenicity to the ECM. These changes may represent another mechanism which contributes to the haemostatic dysfunction observed in uraemic patients.
Nephrol Dial Transplant 1995 Dec
PMID:Uraemic medium causes endothelial cell dysfunction characterized by an alteration of the properties of its subendothelial matrix. 880 11

In summary, abnormalities in lipid and carbohydrate metabolism, including features of the metabolic risk factor syndrome, are frequently present in patients both before and after renal transplantation. Risk factors of atherosclerosis may not only contribute to increased cardiovascular morbidity and mortality in this patient population, but can also be assumed to contribute to the development and progression of CVR and chronic graft dysfunction. For preventing both early graft losses and the development of graft damage leading to late graft dysfunction and graft loss, it appears to be essential to identify patients at risk early, prior to transplantation. Intervention aiming to reduce overweight, diet and exercise may be of benefit. The role of omega-3 unsaturated fatty acid supplementation remains controversial. Pharmacological intervention by antioxidants or agents to reduce lipids and/or decrease PAI-1 synthesis may prove to be beneficial. Early identification of patients at risk and intervention in due time may improve the results of renal transplantation.
Nephrol Dial Transplant 1997 Jan
PMID:Metabolic abnormalities in renal transplant recipients. Risk factors and predictors of chronic graft dysfunction? 902 67

Coronary artery disease and cerebrovascular disease due to the rapid progression of atherosclerosis is the principal cause of death in diabetes mellitus. Modification of low-density lipoproteins (LDL) by advanced glycosylation end-products (AGE) may play a central role in the development of atherosclerosis, especially in diabetic patients. An AGE-modified form of LDL (AGE-LDL) has been found to circulate in human plasma, and AGE modifications have been identified as being present on both the apoprotein (ApoB) and the phospholipid components of LDL. By utilizing an AGE-specific ELISA, we measured the AGE attached to the ApoB and lipid components of LDL from normal controls and diabetic patients with or without end-stage renal disease (ESRD), as well as lipid oxidation. AGE-ApoB, AGE-lipid and oxidized LDL (Ox-LDL) in diabetic patients were significantly higher than those in patients without diabetes. The correlation between AGE-ApoB and AGE-lipid were highly significant. An especially marked elevation of AGE-LDL was found in diabetic patients with ESRD. The correlation between the serum total cholesterol and the AGE-LDL (AGE-ApoB and AGE-lipid) was significant. In addition, based on the known biological properties of AGE-modified peptide (AGE-peptide), we have proposed that these chemically reactive circulating AGE-peptides contribute to tissue injury by reattaching to susceptible target proteins both within and outside the vasculature, and that this process accelerates vascular pathology in diabetic patients. These data indicate that AGE-modified LDLs may represent a particularly atherogenic form of LDL, and AGE-LDLs as well as AGE-peptides are likely to contribute to the development of atherosclerosis in diabetic patients.
Nephrol Dial Transplant 1996
PMID:The role of advanced glycosylation end-products in the pathogenesis of atherosclerosis. 904 4

Oxidative stress is implicated in the pathogenesis of numerous disease processes including diabetes mellitus, atherosclerosis, ischaemia reperfusion injury and rheumatoid arthritis. Chemical modification of amino acids in protein during lipid peroxidation results in the formation of lipoxidation products which may serve as indicators of oxidative stress in vivo. The focus of the studies described here was initially to identify chemical modifications of protein derived exclusively from lipids in order to assess the role of lipid peroxidative damage in the pathogenesis of disease. Malondialdehye (MDA) and 4-hydroxynonenal (HNE) are well characterized oxidation products of polyunsaturated fatty acids on low-density lipoprotein (LDL) and adducts of these compounds have been detected by immunological means in atherosclerotic plaque. Thus, we first developed gas chromatography-mass spectrometry assays for the Schiff base adduct of MDA to lysine, the lysine-MDA-lysine diimine cross-link and the Michael addition product of HNE to lysine. Using these assays, we showed that the concentrations of all three compounds increased significantly in LDL during metal-catalysed oxidation in vitro. The concentration of the advanced glycation end-product N epsilon-(carboxymethyl)lysine (CML) also increased during LDL oxidation, while that of its putative carbohydrate precursor the Amadori compound N epsilon-(1-deoxyfructose-1-yl)lysine did not change, demonstrating that CML is a marker of both glycoxidation and lipoxidation reactions. These results suggest that MDA and HNE adducts to lysine residues should serve as biomarkers of lipid modification resulting from lipid peroxidation reactions, while CML may serve as a biomarker of general oxidative stress resulting from both carbohydrate and lipid oxidation reactions.
Nephrol Dial Transplant 1996
PMID:Lipoxidation products as biomarkers of oxidative damage to proteins during lipid peroxidation reactions. 904 7

Clinical effects of recombinant human erythropoietin (rHuEPO) such as thrombosis, convulsions, hyperviscosity, hypertension, and angiogenic effect in culture cells have been described. We studied the rHuEPO effect on endothelial damage markers and endothelial function markers: tissue-type plasminogen activator (t-PA), nitrate (NO3), thrombomodulin (TM), and von Willebrand factor (vWF). Twenty-six peritoneal dialysis patients treated with rHuEPO and 19 controls were included. The study design for rHuEPO patients consisted of four periods: long-term treatment (rHuEPO-1); 2 months of withdrawal (rHuEPO-2); and 4 months on 5000 IU/week rHuEPO subcutaneously, with markers being measured after 2 months (rHuEPO-3) and after 4 months (rHuEPO-4). After 2 months of rHuEPO withdrawal, a decrease in hemoglobin level appeared (11+/-1.8 g/dL to 9.2+/-1.5 g/dL, p < 0.01). After rHuEPO reintroduction, this value reached 10.6+/-1.5 g/dL at two months, and 11.1+/-1.4 g/dL at four months. A significant increase in t-PA ratio was observed from two months without rHuEPO to two months on rHuEPO, returning to previous values after four months. Similarly, TM increased for patients with creatinine clearances (CrC) < 5 mL/min. No changes in the higher-than-normal plasma vWF levels were found during the various periods. A statistically significant lower value was found in controls compared with rHuEPO-4 patients. A statistically significant increase in NO3 levels was observed in the pre-venous occlusion (VO) test immediately after the re-introduction of rHuEPO. This increment returned to prior values four months after rHuEPO was reintroduced. Our results show that rHuEPO treatment causes an increase in some endothelial damage markers (TM, t-PA) and modifies endothelial function markers (t-PA ratio, NO3). These changes might favor thrombosis and atherosclerosis.
Perit Dial Int 1999
PMID:Effects of recombinant human erythropoietin on functional and injury endothelial markers in peritoneal dialysis patients. 1040 11

Apolipoprotein (Apo) E has an important role in triglyceride (TG)-rich lipoprotein metabolism, and the genotype of Apo E is associated with premature coronary artery disease. Patients undergoing continuous ambulatory peritoneal dialysis (CAPD) develop various abnormalities of lipid metabolism and are prone to develop accelerated atherosclerosis. To investigate the distribution of Apo E genotype, and to evaluate the influence of Apo E polymorphism on lipid metabolism in CAPD patients, we measured Apo E genotypes, serum lipid, and lipoprotein levels in 54 CAPD patients (M:F = 1:1). The most common genotype of Apo E in the CAPD patients was E 3/3, found in 68.5%. The frequencies of the other genotypes were E 2/3, found in 14.8%, and E 4/3, found in 16.7%. No genotypic differences in Apo E were seen in the patients with regard to the presence of diabetes, the level of parathyroid hormone, or the transport characteristics of the peritoneal membrane. When comparing lipid levels by Apo E genotype, the total cholesterol and TG levels of E 2/3 patients were significantly higher than those of E 3/3 or E 4/3 patients. The differences in high-density or low-density lipoprotein cholesterol levels by Apo E genotype were not significant. In comparing lipoprotein levels by Apo E genotype, the Apo B and lipoprotein (a) levels of E 2/3 patients were significantly lower than those of E 3/3 or E 4/3 patients. In conclusion, the Apo E 3/3 genotype seems to be the most common genotype in CAPD patients, and the Apo E 2/3 genotype appears to be associated with high cholesterol and TG levels. These results demonstrate the need for further prospective studies in these subjects aimed at elucidating the impact of genetic variation at the Apo E locus on the development of atherosclerosis.
Adv Perit Dial 1999
PMID:Influence of apolipoprotein E genotype on lipid and lipoprotein levels in continuous ambulatory peritoneal dialysis patients. 1068 11


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