| 1. |
- Arnadottir, Margret, et al.
(författare)
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Adrenocorticotrophic hormone lowers serum Lp(a) and LDL cholesterol concentrations in hemodialysis patients
- 1997
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Ingår i: Kidney International. - : Elsevier BV. - 1523-1755 .- 0085-2538. ; 52:6, s. 1651-1655
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Tidskriftsartikel (refereegranskat)abstract
- Previously, we have shown that short-term administration of adrenocorticotrophic hormone (ACTH) results in reduced concentrations of apolipoprotein B-containing lipoproteins, including lipoprotein(a), and reduced activities of hepatic lipase. These effects were observed in steroid-treated patients suffering from iatrogenic ACTH deficiency and in healthy individuals. The direct nature of the influence of ACTH on hepatic lipoprotein metabolism was confirmed by in vitro experiments. The aim of the present investigation was to study the effects of ACTH treatment on uremic patients, who exhibit disturbed lipoprotein pattern due to the slow removal of triglyceride-rich lipoproteins and who probably are ACTH resistant. Eight patients on chronic hemodialysis were studied. After one intramuscular injection of Synacthen Depot (a synthetic ACTH1-24 preparation from Ciba Geigy AG, Basel, Switzerland) 1 mg, the only change noted was a significant reduction of 26% in median lipoprotein(a) concentration. After five injections, a further decrease (65%) was found in the lipoprotein(a) concentration. Also, reductions in median concentrations of total cholesterol, low density lipoprotein cholesterol and apolipoprotein B were observed. The magnitude of these changes was 15 to 30%. In contrast to previously studied groups, no changes were observed regarding triglyceride metabolism. Significantly increased median concentration of apolipoprotein CIII was found. However, the excess apolipoprotein CIII was confined to the fraction that was not associated with apolipoprotein B. Thus, administration of ACTH to uremic patients improved their atherogenic lipoprotein profile, a fact that may have future therapeutic implications. In comparison to previously studied groups, the uremic patients responded rather slowly and not at all regarding triglyceride metabolism.
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| 2. |
- Arnadottir, Margret, et al.
(författare)
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Corticotropin-induced reduction of plasma lipoprotein(a) concentrations in healthy individuals and hemodialysis patients: relation to apolipoprotein(a) size polymorphism
- 1999
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Ingår i: Metabolism, Clinical and Experimental. - 1532-8600. ; 48:3, s. 342-346
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Tidskriftsartikel (refereegranskat)abstract
- Lipoprotein(a) [Lp(a)], a strong independent cardiovascular risk factor, consists of the unique apolipoprotein(a) [apo(a)] covalently linked to a low-density lipoprotein particle. Apo(a) contains a widely differing number of the plasminogen-like kringle IV, a size polymorphism that is codominantly inherited. In addition to powerful genetic control, renal failure is known to influence the plasma Lp(a) concentration. There is still a lot to be learned about the mode and site of catabolism of Lp(a), and there is no readily applicable Lp(a)-lowering treatment available. Therefore, it was of interest to study further the Lp(a)-lowering effect of corticotropin (ACTH) that has been demonstrated in small studies. The main purpose of the present study was to investigate the influence of ACTH on different apo(a) isoforms. Short-term treatment with ACTH decreased the plasma Lp(a) concentration in all 26 study participants. The two study groups (12 healthy individuals and 14 hemodialysis patients) responded similarly, with a median decrease in plasma Lp(a) of 39% and 49%, respectively. In subjects with two clearly separable apo(a) bands, apo(a) phenotyping and densitometric scanning of the bands before and after treatment with ACTH revealed a change in the proportion of apo(a) isoforms, ie, a shift toward the isoform with lower molecular weight. This was observed in seven of nine investigated subjects (four of five healthy individuals and three of four hemodialysis patients).
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| 3. |
- Arnadottir, Margret, et al.
(författare)
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Effects of short-term treatment with corticotropin on the serum apolipoprotein pattern
- 2001
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Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 61:4, s. 301-306
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with adrenocorticotrophic hormone (ACTH) has a well-documented cholesterol-lowering effect. Increased uptake of low-density lipoprotein (LDL) by HepG2 cells in response to incubation with ACTH has been demonstrated but the precise cholesterol-lowering mechanism has resisted elucidation. Since apolipoproteins are important determinants of lipoprotein metabolism, we sought to extend the knowledge of the effect of ACTH treatment on the serum apolipoprotein (apo) pattern. Twelve healthy individuals and 14 dyslipoproteinemic hemodialysis patients were recruited. The two groups responded similarly to ACTH1-24 at the dose of 1 mg daily for four days. In accordance with previous results, serum concentrations of total cholesterol decreased by 18% and 17%, LDL cholesterol by 25% and 30%, and apo B by 20% and 19%, respectively, while there were no significant changes in the serum concentrations of triglycerides, high-density lipoprotein cholesterol and apo AI. Novel findings were that the serum concentrations of total apo E increased by 48% and 31%, and apo B-associated apo E by 69% and 46%, respectively. Moreover, in the healthy individuals, the serum concentrations of apo CIII did not change in response to ACTH, whereas in the hemodialysis patients, those of apo CIII not associated with apo B increased significantly by 44%. Since apo E binds strongly to the LDL receptor, the present results suggest that the cholesterol-lowering effect of ACTH may be mediated by facilitated hepatic uptake of apo E-enriched apo B-containing lipoproteins. Thus, the findings stimulate further research.
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| 4. |
- Arnadottir, Margret, et al.
(författare)
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Hyperhomocysteinemia in cyclosporine-treated renal transplant recipients
- 1996
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Ingår i: Transplantation. - 1534-6080. ; 61:3, s. 509-512
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Tidskriftsartikel (refereegranskat)abstract
- Moderate hyperhomocysteinemia, an independent cardiovascular risk factor, has been reported in renal transplant recipients. In the present study, plasma concentrations of total homocysteine were significantly increased in 120 renal transplant recipients as compared with 60 healthy controls (19.0 +/- 6.9 vs. 11.6 +/- 2.8 mumol/L, P < 0.0001) and as compared with 53 patients without a transplant but with a comparable degree of renal failure (19.0 +/- 6.9 vs. 16.0 4.9 mumol/L, P < 0.01). There was a significant inverse correlation between glomerular filtration rates and plasma homocysteine concentrations in the renal transplant recipients (r = -0.52, P < 0.0001). Groups of renal transplant recipients, with and without cyclosporine, and renal patients without a transplant were studied; these groups were comparable regarding age, sex distribution, glomerular filtration rate, and folate and vitamin B12 concentrations. Renal transplant recipients on cyclosporine had significantly higher plasma homocysteine concentrations than those not on cyclosporine (19.5 +/- 7.6 vs. 16.2 +/- 4.8 mumol/L, P < 0.05), and the patients without a transplant (19.5 +/- 7.6 vs. 16.0 +/- 4.9 mumol/L, P < 0.01). Thus, the hyperhomocysteinemia of renal transplant recipients not treated with cyclosporine, and that of renal patients without a transplant probably is explained by the same mechanism: renal insufficiency. An additional mechanism seems to operate in renal transplant recipients treated with cyclosporine. The lack of correlation between the concentrations of plasma homocysteine and red cell folate in these patients suggests that cyclosporine interferes with folate-assisted remethylation of homocysteine. Plasma homocysteine concentrations were significantly increased in 24 patients with a history of atherosclerotic complications as compared with the remaining 96 renal transplant recipients (20.8 +/- 4.4 vs. 18.5 +/- 7.3 mumol/L, P < 0.01).
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| 5. |
- Arnadottir, Margret, et al.
(författare)
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Very-low-density lipoprotein of uremic patients is a poor substrate for bovine lipoprotein lipase in vitro
- 1996
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Ingår i: Metabolism, Clinical and Experimental. - 1532-8600. ; 45:6, s. 686-690
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Tidskriftsartikel (refereegranskat)abstract
- Very-low-density lipoprotein (VLDL) from 10 hemodialysis patients and 10 healthy controls was studied with respect to the substrate characteristics for bovine milk lipoprotein lipase (LPL). Compared with the control subjects, the hemodialysis patients had significantly higher serum triglyceride and apolipoprotein B-associated apolipoprotein CIII concentrations (1.03 +/- 0.31 v 1.98 +/- 0.86 mmol/L and 0.004 +/- 0.002 v 0.011 +/- 0.005 g/L, respectively), lower serum high-density lipoprotein (HDL) cholesterol and apolipoprotein AI concentrations (1.33 +/- 0.37 v 0.95 +/- 0.31 mmol/L and 1.29 +/- 0.25 v 1.09 +/- 0.23 g/L, respectively), and lower postheparin plasma LPL activity (82 +/- 24 v 35 +/- 14 milliU/milliL). There were also significant increases in the relative fat content and diameter of VLDL particles from patients versus controls. VLDL was labeled with a fluorescent phospholipid analog, DHPE, and the rate of the lipolytic reaction with purified bovine milk LPL was estimated from the increase in fluorescence intensity at 490 nm. There was no significant difference between initial reaction velocities in the study groups, but VLDL particles from hemodialysis patients were lipolyzed to a significantly lesser extent than those from healthy controls (mean increase in fluorescence intensity after completion of the reaction, 95 +/- 36 v 140 +/- 43 arbitrary units). These results are in accordance with the accumulation of remnant particles reported to occur in uremia despite only a moderately increased serum triglyceride concentration.
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