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- Chevreuil, O, et al.
(författare)
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Biphasic effects of low-molecular-weight and conventional heparins on chylomicron clearance in rats.
- 1993
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Ingår i: Arteriosclerosis and thrombosis : a journal of vascular biology / American Heart Association. - 1049-8834. ; 13:10, s. 1397-403
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Tidskriftsartikel (refereegranskat)abstract
- Chylomicrons labeled in vivo with [14C]triglycerides and [3H]retinyl esters were injected in rats at a series of times after administration of conventional unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), or saline. In saline controls the clearance of both chylomicron triglycerides and retinyl esters seemed to follow exponential courses, with half-lives of about 5 and 10 minutes, respectively. Five minutes after administration of LMWH or UFH, the triglyceride clearance rates were dramatically increased and were associated with an increased appearance of the radiolabel in circulating free fatty acids (FFAs). The clearance of [3H]retinol radioactivity, ie, chylomicron particles, was also enhanced 5 minutes after heparin injection. From 75% to 90% disappeared from the circulation within the first 5 minutes. Their continued disappearance was much slower, with a slope similar to that of the saline-treated rats. Hence, it was as if a new, rapid exponent had been added to the disappearance curve that accounted for most of the particle clearance. Injection of chylomicrons 1 hour after the heparins resulted in substantially slower clearance compared with saline-treated controls of both triglyceride and retinol radioactivity in rats given a high dose of LMWH or a low dose of either heparin. Appearance of label in plasma FFAs was also decreased, suggesting that impeded lipolysis was responsible, at least in part, for the impeded chylomicron clearance. Four and 24 hours after heparin injection all studied parameters of chylomicron clearance had returned to normal.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 2. |
- Chevreuil, O, et al.
(författare)
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Depletion of lipoprotein lipase after heparin administration.
- 1993
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Ingår i: Arteriosclerosis and thrombosis : a journal of vascular biology / American Heart Association. - 1049-8834. ; 13:10, s. 1391-6
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Tidskriftsartikel (refereegranskat)abstract
- Some or most of the turnover of lipoprotein lipase (LPL) occurs by dissociation from vascular endothelial sites in extrahepatic tissues and further degradation in the liver. Heparin greatly enhances this dissociation and delays but does not abolish uptake in the liver, raising the possibility that heparin could lead to accelerated catabolism of functional LPL. To investigate this, we determined time curves for heparin (anti-factor Xa activity) and for LPL and hepatic lipase after injection in rats of two doses of conventional unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). The high dose (250 U/kg) of both heparins resulted in similar initial levels of LPL activity in plasma, but at 30 minutes the activity with LMWH had declined by more than 80%, whereas with UFH it remained essentially unchanged during this time. In contrast, time curves for heparin activity in blood were similar for the two heparins. The low dose (50 U/kg) led to lower initial levels of LPL activity with LMWH in spite of slower elimination of heparin activity from the blood. These results agree with previous studies that indicate that LMWH has a similar ability as UFH to release LPL, but a lesser ability to delay its removal by the liver. Only slight differences were noted in the time curves for hepatic lipase with the two heparins. To assess the possible depletion of the lipases, we administered a second large dose of conventional heparin. One hour after the first injection, the second injection resulted in lower plasma LPL activities in all four groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 3. |
- Liu, G, et al.
(författare)
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Interaction of size-fractionated heparins with lipoprotein lipase and hepatic lipase in the rat.
- 1992
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Ingår i: Biochemical Journal. - 0264-6021 .- 1470-8728. ; 285 ( Pt 3), s. 731-6
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Tidskriftsartikel (refereegranskat)abstract
- Heparin and heparin partially depolymerized by enzymic digestion were separated into six size fractions. Hep 1 (tetrasaccharides), with a mean M(r) of 1200, did not release significant amounts of either lipoprotein lipase (LPL) or hepatic lipase (HL) on intravenous injection into rats. Hep 2 (mainly octa- and deca-saccharides), with a mean M(r) of 2400-3000, released both lipases. To evoke the same plasma activity of LPL and HL required about 10 times more by weight, or about 40 times more molecules, of this heparin than of hep 5 (mean M(r) 12,000, similar to conventional heparin). Hep 5 impeded binding and degradation of 125I-labelled bovine LPL by perfused rat livers. In contrast, hep 2 had no detectable effect on these processes. This demonstrates a difference between the sites in the liver that mediate binding, uptake and degradation of LPL, and the extrahepatic sites that bind functional LPL, and the hepatic sites that bind functional HL. After injection of 3.25 mg of hep 5/kg body weight, plasma LPL activity rapidly rose and then remained high for at least 1 h. With hep 2, plasma LPL also rose rapidly, but then decreased to almost basal by 1 h. When a labelled triacylglycerol emulsion was injected 1 h after the heparins, the fractional catabolic rate was enhanced in the rats that had received conventional heparin, as expected from the high plasma LPL activity, but decreased compared with controls in rats that had received hep 2, indicating that available LPL had been depleted through enhanced transport to and uptake in the liver.
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| 4. |
- Olivecrona, T, et al.
(författare)
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New aspects on heparin and lipoprotein metabolism.
- 1993
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Ingår i: Haemostasis. - 0301-0147 .- 1423-0038. ; 23 Suppl 1, s. 150-60
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Tidskriftsartikel (refereegranskat)abstract
- Lipoprotein lipase (LPL) and hepatic lipase (HL) are two enzymes which participate in metabolism of plasma lipoproteins. The enzymes are located at vascular surfaces and are released from their binding sites on injection of heparin. In this paper we give a short overview of the structure of the lipases and their role in lipoprotein metabolism. Earlier studies had shown that low molecular weight (LMW) heparin preparations result in lower LPL activities in blood than do corresponding amounts of conventional heparin. Studies with organ perfusion in rats show that the two types of heparin have similar ability to release the lipases from their binding sites in extrahepatic tissues, but that LMW heparin is less effective than conventional heparin in preventing rapid uptake and degradation of LPL by the liver. After injection of heparin the metabolism of triglyceride-rich lipoproteins is initially accelerated, presumably as a result of the high levels of circulating LPL. Then follows a phase when lipoprotein metabolism is slower than normal, perhaps because endothelial LPL has been depleted by accelerated transport to and degradation in the liver.
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