Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of cholesteryl ester transfer protein (CETP) was assayed in sera of children and adolescents on continuous ambulatory peritoneal dialysis (CAPD) by coincubating lipoprotein-deficient samples with exogenous donor and acceptor lipoproteins. Serum levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B and apolipoprotein B/apolipoprotein A1 ratio were increased, while the high-density lipoprotein cholesterol level was decreased. The CETP activity in children on CAPD exceeded that in either adults or control children, and was correlated with low-density lipoprotein cholesterol, apolipoprotein B, and total cholesterol/high-density lipoprotein cholesterol, low-density lipoprotein cholesterol/high-density lipoprotein cholesterol, and apolipoprotein B/apolipoprotein A1 ratios. The CETP activity in CAPD patients may be due to increased synthesis in response to a protein loss in the dialysis fluid and may exacerbate atherosclerosis.
Nephron 1996
PMID:Increased activity of plasma cholesteryl ester transfer protein in children with end-stage renal disease receiving continuous ambulatory peritoneal dialysis. 868 32

Administration of puromycin aminonucleoside (PAN) to rats induces acute nephrosis with hyperlipidemia, and, in some experimental conditions, it results in chronic focal glomerulosclerosis. In this study, we examined the cytotoxicity of serum from rats with PAN-induced nephrosis, since hypercholesterolemia is considered to cause injury to vascular walls in atherosclerosis, the mechanism of which is analogous to that of glomerulosclerosis. About half of the tested sera from nephrotic rats (9 out of 17) were cytotoxic to cultured aortic endothelial cells. The toxic substance(s) was heat-stable and was extracted in the lipid fraction. Serum levels of triglyceride and cholesterol were markedly higher in the group of rats with cytotoxic serum than in the group with noncytotoxic serum. No cytotoxicity was associated with sera from control rats or the corresponding lipid fractions. Cytotoxic sera were also effective against cultured glomerular epithelial and mesangial cells. These results indicate that cytotoxic lipid is produced in rats with PAN nephrosis and the results raise the possibility that the cytotoxic lipid in nephrotic serum might contribute to lipid-mediated glomerular injury which may induce glomerulosclerosis at a subsequent stage.
Nephron 1996
PMID:Cytotoxicity of sera from rats with puromycin aminonucleoside nephrosis. 877 53

Noradrenaline (NA)-containing nerves, mainly originating in the sympathetic superior cervical ganglia, supply large and small cerebral arteries. In large cerebral arteries, nerves containing serotonin (5-hydroxytryptamine, 5-HT) may represent neuronal uptake of circulating 5-HT by sympathetic nerves. 5-HT-containing nerves supplying small pial vessels probably have a central origin in the dorsal raphe nucleus. In most species, NA is a weak vasoconstrictor (alpha 1- or alpha 2-adrenoceptors), while 5-HT is a potent vasoconstrictor (5-HT2 or 5-HT1-like receptors) of large cerebral arteries. In contrast, both NA and 5-HT tend to cause vasodilatation in small pial vessels and arterioles. Adrenergic and serotonergic transmission can be modulated by pH, a range of putative neurotransmitters and neuromodulators, and by the endothelium. Sumatriptan, a 5-HT1-like receptor agonist, has been shown to be effective in the treatment of migraine. Changes in NA- or 5-HT-containing nerves and/or in the responses of cerebral vessels to NA and 5-HT have been observed in a variety of vascular disorders, including cerebral vasospasm following subarachnoid haemorrhage, hypertension, and atherosclerosis.
 ...
PMID:Innervation of cerebral arteries by nerves containing 5-hydroxytryptamine and noradrenaline. 878 67

Renal disease patients often exhibit alterations in the lipid profile which may become an important risk of accelerated atherosclerosis and contribute to disease progression. Among such alterations, increased levels of lipoprotein(a) [Lp(a)] are common and may be related, in part, to the degree of proteinuria. Omega-3 polyunsaturated fatty acids (omega-3 FA) have been reported to decrease Lp(a) concentrations in nonrenal subjects. In addition, they have recently been shown to reduce proteinuria in patients with chronic glomerular disease. We therefore tested the hypothesis that omega-3 FA treatment in patients with chronic glomerular disease may reduce Lp(a) concentrations. Eight patients (2 with membranous glomerulonephritis, 6 with focal glomerular sclerosis) were submitted to a total of 13 six-week courses of treatment with omega-3 FA, at a dose of 3 g/day with a triglyceride preparation (n = 4) and of 7.7 g/day with an ethyl-ester preparation (n = 9). Both treatments significantly increased the proportions of omega-3 to omega-6 FA in total serum lipids, documenting compliance to treatment. Both treatments were also effective in decreasing serum thromboxane (from mean 490 +/- (SEM) 70 to 325 +/- 49 ng/ml, p < 0.05, in the high-dose group) and prolonging the bleeding time (from 5.8 +/- 0.4 to 7.7 +/- 0.5 min, p < 0.05, in the high-dose group), thus documenting the biological efficacy of treatment. However, despite a significant reduction in serum triglyceride levels (from 137 +/- 20 to 104 +/- 19 mg/dl in the high-dose group), Lp(a) concentrations did not change (292 +/- 120 U/l before, 315 +/- 130 U/l after the high-dose therapy). Treatment-related changes in proteinuria (from 2.9 +/- 0.5 to 2.1 +/- 0.7 g/24 h) were not related at all to changes in Lp(a) levels. We conclude that omega-3 FA do not decrease Lp(a) concentrations in renal patients with chronic glomerular diseases and that Lp(a) levels are unlikely to be related to the degree of proteinuria within the short-term modifications induced by omega-3 FA.
Nephron 1996
PMID:Omega-3 fatty acid supplementation and lipoprotein(a) concentrations in patients with chronic glomerular diseases. 885 84

At present, there are very few studies that look at the effect of uremia, prednisone and cyclosporine therapy on the lipid profiles of children. This effect is important because of the potential association of hyperlipidemia and increased risk of cardiovascular morbidity and mortality and glomerulosclerosis. We measured fasting lipid profiles in 73 children. There were 21 controls, 18 patients treated with cyclosporine and prednisone, 9 patients treated with cyclosporine alone and 25 dialysis patients. Lipoprotein (a) levels were measured using direct binding 'sandwich' ELISA. Uremic children had higher levels of triglycerides and very-low-density lipoprotein as compared with the control group. Children receiving combination of cyclosporine and prednisone also had higher total cholesterol, triglycerides, low-density lipoprotein, very-low-density lipoprotein as compared to the control group. However, children receiving cyclosporine monotherapy had lipid profiles similar to the control group. Patients receiving cyclosporine and prednisone had higher total cholesterol, high-density lipoprotein and low-density lipoprotein as compared with the dialysis group. Evaluating lipoprotein (a) levels, children on cyclosporine monotherapy had lower lipoprotein (a) levels as compared with children on dialysis and those receiving both combination therapy. The total cholesterol/high-density lipoprotein-cholesterol ratio (TC/HDL) was similar among the study groups. In summary, uremic children and children receiving steroids with cyclosporine have elevated lipid levels. However, the increased risk for atherosclerosis is not evident because of similar levels of lipoprotein (a) and TC/HDL ratios among the study groups.
Nephron 1996
PMID:Hyperlipidemia in children: the role of uremia, steroids and cyclosporine therapy. 893 76

Recently, involvement of remnant-like particle cholesterol (RLP-C) in atherosclerosis was reported, but this parameter has not been adequately investigated in hemodialysis (HD) patients. The present study investigated the relationship between the RLP-C level and total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), lipid peroxides (malone dialdehyde, MDA), apolipoprotein (Apo) A-I, and ApoB. In addition, the fractions of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), LDL, and HDL in serum lipoproteins were determined by disk polyacrylamide gel electrophoresis. The relationship between the RLP-C level and three atherogenic indices was also studied. The RLP-C level in HD patients (8.2 +/- 6.7 mg/dl) was significantly higher than that in normal controls (2.7 +/- 1.3 mg/dl). The RLP-C level showed a significant positive correlation with the levels of TC, TG, LDL-C, MDA, ApoB, VLDL(%), and IDL(%), as well as a negative correlation with HDL(%). However, there was no correlation with age or the duration of HD. RLP-C also showed significant positive correlations with the (TC -HDL-C)/HDL-C ratio and the (VLDL + LDL)/HDL ratio, as well as a negative correlation with the ApoA-I/ApoB ratio. These results suggest that RLP-C may be a potential indicator of atherogenic risk in HD patients.
Nephron 1997
PMID:Remnant-like particle cholesterol may indicate atherogenic risk in patients on chronic hemodialysis. 917 Dec 93

The accelerated arteriosclerosis of chronic dialysis patients is multifactorial. Both non-uremic patients with atherosclerosis and uremic patients have functional platelet abnormalities. Our aim was to study platelet function in chronic dialysis patients and to correlate the findings with the presence of cardiovascular morbidity. Fifty-three chronic dialysis patients were examined. The presence of risk factors for cardiovascular disease (CVD) was recorded, and the patients were examined for the presence of ischemic heart disease, peripheral vascular disease and cerebrovascular accident. The parameters of platelet function, which were examined with the modified Wu and Hoak method, included platelet number, percentage of totally, reversibly and irreversibly aggregated platelets, average number of platelets per aggregate and percentage of large platelets. Significant differences were found between totally aggregated platelets, reversibly and irreversibly aggregated platelets, the percentage of large platelets (p < 0.0001) and the average number of platelets per aggregate (p < 0.001) in dialysis patients compared with control persons. There was no difference between the 2 groups in platelet count. No differences were found between hemodialysis and peritoneal dialysis groups, and the duration of dialysis treatment had no effect. We conclude that platelet abnormalities evident in chronic dialysis patients are a part of the multifactorial etiology of advanced CVD and may predispose dialysis patients to CVD.
Nephron 1997
PMID:Circulating aggregated platelets, number of platelets per aggregate and platelet size in chronic dialysis patients. 938 Feb 37

Low-voltage-activated T-type Ca2+ channels are present in most excitable tissues including the heart (mainly pacemaker cells), smooth muscle, central and peripheral nervous systems, and endocrine tissues, but also in non-excitable cells, such as osteoblasts, fibroblasts, glial cells, etc. Although they comprise a slightly heterogeneous population, these channels share many defining characteristics: small conductance (< 10 pS), similar Ca2+ and Ba2+ permeabilities, slow deactivation, and a voltage-dependent inactivation rate. In addition, activation at low voltages, rapid inactivation, and blockade by Ni2+ are classical properties of T-type Ca2+ channels, which are less specific. T-type Ca2+ channels are weakly blocked by standard Ca2+ antagonists. Pharmacological blockers are scarce and often lack specificity and/or potency. The physiological modulation of T-type Ca2+ currents is complex: they are enhanced by endothelin-1, angiotensin II (AT1-receptor), ATP, and isoproterenol (cAMP-independent), but are reduced by angiotensin II (AT2-receptor), somatostatin and atrial natriuretic peptide. Norepinephrine enhances these currents in some cells but decreases them in others. T-type Ca2+ currents have many known or suggested physiological and pathophysiological roles in growth (protein synthesis, cell differentiation, and proliferation), neuronal firing regulation, some aspects of genetic hypertension, cardiac hypertrophy, cardiac fibrosis, cardiac rhythm (normal and abnormal), and atherosclerosis. Mibefradil is a new Ca2+ antagonist that is effective in hypertension and angina pectoris. Its favorable pharmacological profile and limited side effects appear to be related to selective block of T-type Ca2+ channels: mibefradil reduces vascular resistance and heart rate without negative inotropy or neurohormonal stimulation, and it also has significant antiproliferative actions.
 ...
PMID:T-type Ca2+ channels and pharmacological blockade: potential pathophysiological relevance. 951 67

Cardiovascular disease is the major cause of morbidity and mortality in patients with end-stage renal failure. Increased free radical production and antioxidant depletion may contribute to the greatly increased risk of atherosclerosis in these patients. Glutathione peroxidase (GPX) is an important antioxidant, the plasma form of which is synthesized mainly in the kidney (eGPX). The aim of this study was to assess the activity of eGPX in patients with end-stage renal failure on haemodialysis. Venous blood was collected from 87 haemodialysis patients immediately prior to and after dialysis and from 70 healthy controls. Serum eGPX activity was measured using hydrogen peroxide as substrate and immunoreactivity determined by ELISA. eGPX activity was significantly reduced in dialysis patients when compared to controls (106 +/- 2.7 and 281 +/- 3.6 U/l respectively, p < 0.001). Following haemodialysis, eGPX activity rose significantly to 146 +/- 3.8 U/l, p < 0.001, although remaining below control values (p < 0.005). Immunoreactive eGPX, however, was similar in all groups (pre-dialysis 14.10 +/- 1.26 microg/ml, post-dialysis 14.58 +/- 1.35 microg/ml, controls 15.20 +/- 1.62 microg/ml, p = NS). A decrease was observed in the specific activity of eGPX in patients when compared to controls (8.81 +/- 1.14, 10.71 +/- 1.54 and 21.97 +/- 1.68 U/mg respectively, p < 0.0001). eGPX activity is impaired in patients undergoing haemodialysis and so may contribute to atherogenesis in renal failure.
Nephron 1999
PMID:Plasma glutathione peroxidase activity is reduced in haemodialysis patients. 1072 Sep 2

Serum paraoxonase (PON) is a high-density lipoprotein (HDL)-associated hydrolase, which inhibits low-density lipoprotein oxidation. Uremic and kidney-transplanted patients have an increased risk of atherosclerosis, to which an increased lipoprotein oxidation may contribute. The aim of our study was to determine whether the PON activity or phenotype is altered in uremic and kidney-transplanted patients, and to compare the values with those of healthy controls. 117 uremic patients on long-term hemodialysis treatment, 115 renal-transplanted patients, and 110 healthy controls were involved in the study. The PON activity was significantly reduced in the uremic patients compared to controls (PON 101.36+/-30. 12 vs. control 188.05+/-58.96 U/ml; p < 0.001), while in kidney-transplanted patients the values were almost identical to those of controls (PON 161.5+/-35.39 U/ml). The different immunosuppressive drug combinations did not influence PON activity. To assess whether the altered PON activity was due to a decrease HDL level, we standardized the enzyme activity for the HDL concentration (PON/HDL ratio). We found that the standardized enzyme activity was lower in the uremic (102.7+/-54.8) and kidney-transplanted patients (144.5+/-32.7) when compared to controls (194.5+/-94.5; p < 0.001). The phenotypic distribution of PON in uremic, renal transplant and control patients are as follows: AA 66.67, 56.48 and 66.67%; AB 31. 62, 33.3 and 26.67%; BB 1.71, 10.19 and 6.67%. We conclude that the decreased PON/HDL and PON/apoA-1 ratios may lead to a reduction in the antioxidant capacity of HDL, which might contribute to the accelerated development of atherosclerosis in uremic and kidney-transplanted patients.
Nephron 1999
PMID:Serum paraoxonase activity changes in uremic and kidney-transplanted patients. 1051 91


<< Previous 1 2 3 4 5 6 7 8 Next >>