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)

Patients with renal failure on maintenance hemodialysis have accelerated rate of atherosclerosis. This, and the fact that chemically modified low-density lipoproteins (LDL) have a better capacity than native LDL to stimulate cholesteryl ester accumulation within macrophages in the vessel wall, led us to examine the possibility that some alteration in apo-LDL may take place in chronically uremic patients. We isolated LDL (d = 1.019 - 1.063 g/mL) from 18 patients with chronic renal failure and from 13 normolipidemic controls and compared the interactive properties of the different LDL preparations with cultured fibroblasts. Our results show that "uremic" LDL associates less, is degraded less, and has diminished ability to stimulate cholesteryl ester formation in fibroblasts when compared to normal LDL. LDL carbamylated in vitro showed interactive properties with fibroblasts similar to those of uremic LDL. Uremic LDL was not taken up by scavenger receptors present on rat peritoneal macrophages, similarly to normal LDL. However, the decrease in uptake by fibroblasts of uremic LDL may increase the residence time of these particles within the subendothelial region of the vessel wall, ultimately resulting in increased atherogenicity. Carbamylation of lysine residues of apoB in vivo, abnormal catabolism of LDL due to the absence of functional renal tissue, or triglyceride enrichment of LDL are among the possible explanations for the abnormal properties of uremic LDL.
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PMID:Abnormal cell-interactive properties of low-density lipoproteins isolated from patients with chronic renal failure. 396 57

In rabbits with chronic renal failure of 9 months' duration, the distribution and morphological characteristics of uremic arterial disease were investigated, with special reference to the coronary arteries. All major systemic arteries were affected, large vessels more severely than smaller ones, and within each artery the changes were most pronounced in the proximal part of the vessel. The intimal lesions consisted primarily of smooth muscle cells without calcification or lipid accumulation. A reduction of the lumen exceeding 50% of the normal cross sectional area was not seen and mural thrombosis was not encountered. In the media, degenerative changes with increased amounts of proteoglycans and calcifications were prominent, but foci of increased cellularity were also seen. There was no evidence of lipid accumulation in the media either. Similar changes were found in the coronary arteries, but coronary angiography revealed no irregularities or stenosis. The calcified medial degenerative changes and intimal cellular lesions without lipid accumulation in non-cholesterol-fed rabbits distinguish uremic arterial disease from atherosclerosis.
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PMID:Uremic arterial disease in rabbits with special reference to the coronary arteries. 398 38

The metabolic remnants of triglyceride-rich lipoproteins are atherogenic in man and experimental animals. Particles resembling lipoprotein remnants have been found in plasma from patients with chronic renal failure (CRF). In this study we took advantage of the observation that retinyl esters are transported only by lipoproteins that originate in the intestine, that is, by chylomicrons (CM) and their remnants. To investigate further remnant metabolism in CRF, plasma RE were measured by reverse-phase high performance liquid chromatography in 20 non-diabetic hemodialyzed patients with CRF and 20 hospitalized non-diabetic control subjects 12-15 h after the administration of retinyl ester, 25000 IU orally. Total plasma RE were increased 3-fold in the CRF patients (P less than 0.001). Quantitative analysis of retinoids and lipids in fractions separated by unit-gravity flotation and flocculation in 3% polyvinylpyrrolidone indicated that the plasma RE were not contained among intact CM. Mean plasma retinol in CRF was also elevated consistent with previous observations and the known role of the kidney in retinol-binding protein metabolism. Although postabsorptive RE concentration was correlated positively and significantly with plasma triglyceride concentration in both groups, RE were higher in CRF patients at comparable plasma triglyceride concentrations. These data support the proposal that atherogenic lipoprotein remnants accumulate in the plasma of patients with CRF.
Atherosclerosis 1985 Nov
PMID:Retinyl ester retention in chronic renal failure. Further evidence for a defect in chylomicron remnant metabolism. 408 53

The relation between chronic renal failure and the clinical and histological findings in normal-looking skin was studied in twenty-seven patients with minimum to marked rises of serum creatinine; eleven of these were on maintenance haemodialysis, and three were successful renal transplant recipients. Clinical findings, including pruritus and xerosis which affected 48% and 60%, respectively, of the patients overall, correlated strongly with severity of renal failure. Histological examination revealed endothelial cell activation and/or necrosis, basement membrane zone thickening, and reduplication of the basal lamina involving both venules and arterioles in all specimens. The microangiopathy was severe in 18 of 24 (75%) of the uraemic specimens, but severity correlated poorly with serum creatinine level, haemodialysis status, or known duration of renal failure, except that it was less severe in the first 2 years (p < 0.02). In contrast, the microangiopathy was very much less severe in the transplant recipients than in haemodialysed patients (p < 0.02) and, in the patient studied both before and after transplantation, changes regressed from severe to moderate within 2 months of transplantation. Other histological findings present in many specimens did not correlate with vessel changes. The findings establish the existence of a potentially reversible microangiopathy in normal-looking skin of patients with chronic renal failure. Further study is needed to determine if it reflects the same pathological process that underlies the development of accelerated atherosclerosis responsible for about half the deaths among patients on maintenance haemodialysis.
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PMID:Clinical and histological skin changes in chronic renal failure: evidence for a dialysis-resistant, transplant-responsive microangiopathy. 610 48

The composition and concentration of remnant lipoprotein particles accumulating in the plasma of patients with chronic renal failure (CRF) was determined. Ten patients on chronic hemodialysis were compared with 8 controls. The patients' very low density lipoproteins (VLDL) were abnormal and contained more of the dense VLDL subfraction (VLDL3). The concentration of intermediate density lipoproteins (IDL) was increased 3-fold in CRF plasma, whereas the amount of low density lipoprotein (LDL) was decreased by 25%. On electrophoresis of plasma lipoproteins the beta-band from the patients' samples demonstrated increased anodal mobility, indicating an abnormality in composition of the patients' LDL. These abnormalities were present regardless of whether patients were hyperlipidemic or not. These findings suggest defective conversion of VLDL to LDL in CRF, allowing for the accumulation of lipoprotein particles usually absent from plasma. The latter may account for the accelerated atherosclerosis reported in patients with CRF.
Atherosclerosis 1983 Jan
PMID:Accumulation of lipoprotein remnants in patients with chronic renal failure. 683 95

The generation of thromboxane B2 (TxB2) from its natural precursor, arachidonic acid, was studied in vitro in order to assess further the prostaglandin pathway in the platelets of patients with chronic renal failure. Some, but not all patients with conservatively treated uraemia synthesised significantly less TxB2 then controls and the same patients were also hypo-aggregable to arachidonic acid. The synthesis of TxB2 appeared normal in a group of patients on chronic ambulatory peritoneal dialysis (CAPD). In contrast, a group of patients on long-term maintenance haemodialysis produced significantly greater amounts of TxB2 and were hyper-aggregable to arachidonic acid, a finding which may be relevant to the high incidence of atherosclerosis and vascular disease in these patients.
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PMID:Synthesis of thromboxane B2 in uraemia and the effects of dialysis. 686 24

The effects of chronic renal failure (CRF) and corticosteroid treatment on the aortic uptake of labelled free and esterified cholesterol (FC and EC) were investigated in normocholesterolemic rabbits. Methylprednisolone, 0.4 mg/day, or placebo was administered for 14 weeks to rabbits with normal renal function and with CRF. Then [3H]- and [14C]cholesterol were administered intravenously and orally, respectively. The radioactivity levels of FC and EC in plasma were measured at regular intervals. After 48 h the accumulation of 3H and 14C radioactivity of FC and EC in the intima-media of the thoracic aorta was determined. An aortic uptake coefficient was calculated by dividing the tissue radioactivity (dpm/cm2/h) by the mean plasma radioactivity (dpm/ml). The mean uptake coefficient of EC in normal rabbits was 6 nl/cm2/h, the value for FC being 180 nl/cm2/h. In normal rabbits treated with methylprednisolone the uptake coefficients of both FC and EC were significantly decreased to about 50% of the values in normal rabbits receiving placebo. A similar significant decrease in the uptake coefficients was found in the CRF rabbits receiving placebo. No further decrease was observed in the CRF rabbits treated with methylprednisolone. The cholesterol content of the aortic intima-media was significantly decreased only in CRF rabbits on methylprednisolone treatment. The results do not indicate an acceleration of uremic arterial disease by steroid treatment in the rabbit.
Atherosclerosis 1983 May
PMID:Effect of chronic renal failure and methylprednisolone treatment on the uptake of labelled plasma cholesterol into the aorta of normocholesterolemic rabbits. 687 Oct

Concentrations of peptidic compounds in blood plasma of uremics are increased. Evidence for participation of intestinal bacteria in the production of such peptides (presumably toxic) was obtained by isolation of a strongly basic peptide containing covalently bound spermidine from peritoneal dialysate of patients with chronic uremia. The same peptide was found in blood plasma of patients with end-stage chronic renal failure. The absence of glutamic acid in the spermidinepeptide molecule suggests that an enzyme different from the transglutaminase of mammalian cells must take part in the synthesis of spermidinepeptide. This conjugate forms a relatively stable complex with insulin, thus altering the action of the hormone on adipose cell metabolism. Also, interaction of spermidinepeptide with insulin and lipoproteins may contribute to hypertriglyceridemia and accelerated atherosclerosis in patients with chronic uremia.
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PMID:A uremic peptide containing polyamine: formation and possible role in uremic hypertriglyceridemia. 701 Mar 92

We have analysed the fatty acid composition of serum cholesterol esters (CE), phospholipids (PL) and triglycerides (TG) and of adipose tissue (AT) lipids in 72 males and chronic renal failure (CRF). Sixteen patients were treated with protein-poor diet. 16 with hemodialysis. The results have been related to clinical aspects of the disease and to abnormalities in serum lipid and lipoprotein concentrations. The major findings were high relative content of oleic acid and a low relative content of linoleic acid in all lipids in the diet-treated group compared to both controls and to the untreated and dialysed patients. Tendencies in the same directions were seen also in the untreated subjects, significant for oleic and linoleic acid in CE and for oleic acid in PL. These changes did not correlate to serum of lipoprotein lipids, or to serum creatinine concentrations in patients not on diet or dialysis, indicating that other factors are more important in modifying the fatty acid metabolism in CRF. The composition of the protein-poor diet, which was rich in fat but low in linoleic acid in relation to oleic acid, is probably a major factor explaining our findings in the diet-treated group. Since low levels of linoleic acid in plasma and AT lipids have been suggested to be a risk factor for atherosclerosis, more attention should be paid to the content and composition of dietary fat in order to prevent the occurrence of such low levels.
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PMID:Fatty acid composition of serum and adipose tissue lipids in males with chronic renal failure. Relations to serum lipoproteins and clinical factors. 707 24

Since accelerated atherosclerosis may be induced by excess circulating remnants of triglyceride-rich lipoprotein catabolism, we looked for evidence of remnant particle accumulation in the lipoproteins of 11 patients on long-term dialysis. We found several abnormalities in lipoprotein protein and lipids: enrichment of intermediate-density lipoproteins (ILD) and low-density lipoproteins (LDL) with triglyceride; the presence of apoprotein B48 (a "marker" for intestinal lipoproteins) in very-low-density lipoproteins (VLDL); an increased concentration of apoprotein AIV (a protein related to chylomicron transport); the presence of AIV in VLDL, IDL, and LDL; and the presence in LDL of apoproteins C and E (proteins not normally found in LDL). These findings strongly suggest accumulation of remnants of triglyceride-rich lipoproteins in patients with chronic renal failure who are undergoing peritoneal dialysis or hemodialysis, and may explain in part the increased incidence of coronary deaths among these patients.
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PMID:Increased lipoprotein-remnant formation in chronic renal failure. 708 97


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