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Biomedical subjects

T Olivecrona

Publications and source records attributed to T Olivecrona.

At least 55 records · Page 3Linked to original sources
PubMed1993

Composition of human low density lipoprotein: effects of postprandial triglyceride-rich lipoproteins, lipoprotein lipase, hepatic lipase and cholesteryl ester transfer protein.

A preponderance of small, dense low density lipoprotein (LDL) particles has been linked to increased risk of myocardial infarction, and a dense and protein-rich LDL has proved to be a characteristic of patients with manifest coronary heart disease (CHD). The present study focused on metabolic determinants of the LDL subfraction distribution with the emphasis placed on alimentary lipaemia. The relations of plasma levels and composition of light (1.019 < d < 1.040 kg/l) and dense (1.040 < d < 1.063 kg/l) LDL subfractions to postprandial triglyceride-rich lipoproteins (TGRL), postheparin plasma lipase activities and the activity of cholesteryl ester transfer protein (CETP) were studied in 32 men with angiographically ascertained premature coronary atherosclerosis (age 48.8 +/- 3.2 years) and in 10 age matched healthy control men. LDL subfractions were separated by equilibrium density gradient ultracentrifugation of fasting plasma drawn before participants were subjected to an oral fat tolerance test of a mixed meal type. The response of TGRL to the oral fat load was determined by measuring plasma triglycerides, and the apolipoprotein (apo) B-48 and apo B-100 content of Sf 60-400 and Sf 20-60 lipoprotein fractions. At a second visit plasma samples were taken for determination of postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities and for measurement of CETP activity. Hypertriglyceridaemic patients had a preponderance of dense LDL particles compared with normotriglyceridaemic patients and controls. The magnitude of the response of TGRL to the oral fat load showed a positive association with the dense LDL apo B concentration (r = 0.32-0.52, P < 0.05), whereas the LPL activity correlated positively with the free (r = 0.50, P < 0.001) and esterified cholesterol (r = 0.45, P < 0.01) and apo B (r = 0.42, P < 0.01) content of the light LDL fraction. The HL activity was found to be inversely associated with the plasma level of light LDL triglycerides (r = -0.38, P < 0.05). In contrast, no relations were noted between CETP activity and plasma concentrations of LDL constituents. Multiple stepwise linear regression analysis with the proportion of total LDL apo B contained in the dense LDL subfraction (% dense LDL apo B) used as the dependent variable indicated that the combined effect of LPL activity and postprandial plasma levels of TGRL (areas under the curve for plasma triglycerides or Sf 60-400 apo B-48) accounted for around 50% of the variability in the distribution of LDL particles between light and dense subfractions.(ABSTRACT TRUNCATED AT 400 WORDS)

Carrier Proteins↗
PubMed1993

Human intestinal alkaline phosphatase--release to the blood is linked to lipid absorption, but removal from the blood is not linked to lipoprotein clearance.

To evaluate a possible quantitative relationship between the rise in intestinal alkaline phosphatase (IAP) activity and triglyceride-rich lipoproteins in the blood after an oral fat intake, a specific and sensitive immunocatalytic assay was used. First, day to day variation of the basal IAP activity in the blood of eight volunteers was evaluated. One group of subjects with high basal IAP activity and great variations from one day to the other was distinguished from a group with low basal IAP activity and small day to day variations. The subjects with high basal IAP activities were all secretors of red blood cell antigens, while those with low basal IAP activities were non-secretors. The IAP activity in the blood rose after fat rich meals but not after fat free meals. To further investigate this, IAP activities were measured in the blood of 28 men before 3, 6, 9 and 12 h after a standardized oral fat load of a mixed meal type. The activity rose in all individuals and showed a similar time course as the rise in plasma TG concentration. The elevations of the IAP activity were, however, not quantitatively correlated with the elevations in TG concentration, nor were there any relations in time to peak levels. Subjects with high basal IAP increased their IAP activity more than those with low basal IAP, but within neither group there was any correlation between the basal IAP activity and the rise in IAP activity. IAP did not float with lipoproteins on ultracentrifugation of plasma, nor did IAP bind to lipid droplets from a fat emulsion added to plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Changes in biological activity and immunoreactive mass of lipoprotein lipase in congenital nephrosis: relationship to hypertriglyceridaemia.

The major lipid disturbance in children with congenital nephrosis of the Finnish type (CNF) is hypertriglyceridaemia. To determine whether or not hypertriglyceridaemia is caused by defective triglyceride catabolism, we measured lipoprotein lipase (LPL) activities and masses at various stages of the disease. At age 3 months in CNF both LPL activity and mass were decreased, but a close positive correlation between these parameters similar to that in controls was observed. At age 9 months both LPL activity and mass were even lower. At that time a significant positive correlation (r = 0.72, P < 0.05) between LPL activities and albumin concentrations and significant negative correlations between plasma free fatty acid (FFA) concentrations and LPL activities (r = -0.72, P < 0.05) and between plasma FFA concentrations and serum albumin concentrations (r = -0.73, P < 0.05) were observed, suggesting that low albumin concentrations result in increase of FFA levels, which could interfere with a normal LPL function at the endothelial surface. On dialysis after nephrectomy, LPL activities and masses increased. At age 3 and 9 months apoprotein C-II (apo C-II) and apoprotein C-III (apo C-III) levels were not decreased although apoproteins were being lost into the urine. On dialysis the mean ratio of apo C-II/C-III was significantly lower than the mean in controls (P < 0.001). We conclude that impaired function of LPL seems to be the major cause of hypertriglyceridaemia and disintegrity of the VLDL-IDL-LDL delipidation cascade in children with CNF.

Apolipoprotein C-II↗
PubMed1993

New aspects on heparin and lipoprotein metabolism.

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.

Animals↗
PubMed1993

Depletion of lipoprotein lipase after heparin administration.

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)

Animals↗
PubMed1993

Biphasic effects of low-molecular-weight and conventional heparins on chylomicron clearance in rats.

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)

Animals↗
PubMed1993

Metabolism of triglyceride-rich lipoproteins during alimentary lipemia.

The metabolism of chylomicron remnants and VLDL was studied in healthy controls and normo- (NTG) and hypertriglyceridemic (HTG) patients with coronary artery disease after intake of an oral fat load. Specific determination of apo B-48 and B-100 enabled separation of the respective contribution of the two lipoprotein species. The postprandial plasma levels of small (Sf 20-60) and large (Sf 60-400) chylomicron remnants increased in controls and NTG patients. In contrast, only large chylomicron remnants increased in the HTG patients. An increase of large VLDL was seen in response to the oral fat load in all groups, whereas small VLDL were either unchanged in the controls and the NTG patients, or decreased in the HTG patient group. The whole plasma concentration of C apolipoproteins was essentially uninfluenced by the oral fat load, whereas the content in large triglyceride-rich lipoproteins paralleled the apo B elevations in controls and NTG patients. An even more prominent increase of apo B in large triglyceride-rich lipoproteins in the HTG group was not accompanied by an increase of C apolipoproteins. These findings indicate that chylomicrons compete with VLDL for removal of triglycerides by lipoprotein lipase and that the postprandial metabolism of triglyceride-rich lipoproteins is severely defective in hypertriglyceridemia.

Apolipoproteins B↗
PubMed1993

Lipoprotein lipase in human plasma is mainly inactive and associated with cholesterol-rich lipoproteins.

This study was designed to further ascertain the presence in plasma of lipoprotein lipase (LPL) bound to circulating lipoproteins. Lipoprotein lipase mass and activity values in preheparin plasma from 20 volunteers were 69.8 +/- 6.6 ng.ml-1 and 1.54 +/- 0.15 mU.ml-1, respectively, and no significant correlation between mass and activity was observed. Fifteen min after heparin injection, LPL mass had increased to 536 +/- 60 ng.ml-1 and LPL activity to 261 +/- 34 mU.ml-1 and a highly significant correlation between the increments in mass and activity was observed. The released material had a specific activity of 0.57 +/- 0.03 mU.ng-1. The LPL mass in preheparin plasma eluted early from heparin-Sepharose, in the position expected for inactive LPL monomers. Western blot analysis showed that the eluted material had the size expected for the LPL subunit (55 kDa). The increment of mass and activity after heparin eluted later from heparin-Sepharose, in the position expected for active LPL dimers. It is concluded that preheparin plasma contains substantial amounts of inactive LPL protein, and that heparin releases mainly active LPL into circulation. On gel filtration LPL activity and mass in postheparin plasma eluted mainly in the positions of LDL and HDL. Electron microscopy of immunostained fractions showed reaction for LPL and apolipoprotein B, or apolipoprotein A-I, on the same particles. LPL mass in preheparin plasma eluted in a similar pattern, associated with LDL and HDL. In postprandial plasma substantial amounts of LPL protein eluted with the triglyceride-rich lipoproteins. When 125I-labeled bovine LPL was added to plasma or to ultracentrifugally isolated lipoproteins and then analyzed by gradient gel electrophoresis, the labeled lipase moved with the lipoproteins. The presence of substantial amounts of inactive LPL protein associated with lipoproteins in plasma may have important implications for the metabolism of the particles in view of recent reports on avid binding of LPL-lipoprotein complexes to cell surfaces and receptors.

Apolipoproteins↗
PubMed1992

Triacylglycerol and phospholipid hydrolysis in human plasma lipoproteins: role of lipoprotein and hepatic lipase.

To explore the interactions of triacylglycerol and phospholipid hydrolysis in lipoprotein conversions and remodeling, we compared the activities of lipoprotein and hepatic lipases on human VLDL, IDL, LDL, and HDL2. Triacylglycerol and phospholipid hydrolysis by each enzyme were measured concomitantly in each lipoprotein class by measuring hydrolysis of [14C]triolein and [3H]dipalmitoylphosphatidylcholine incorporated into each lipoprotein by lipid transfer processes. Hepatic lipase was 2-3 times more efficient than lipoprotein lipase at hydrolyzing phospholipid both in absolute terms and in relation to triacylglycerol hydrolysis in all lipoproteins. The relationship between phospholipid hydrolysis and triacylglycerol hydrolysis was generally linear until half of particle triacylglycerol was hydrolyzed. For either enzyme acting on a single lipoprotein fraction, the degree of phosphohydrolysis closely correlated with triacylglycerol hydrolysis and was largely independent of the kinetics of hydrolysis, suggesting that triacylglycerol removed from a lipoprotein core is an important determinant of phospholipid removal via hydrolysis by the lipase. Phospholipid hydrolysis relative to triacylglycerol hydrolysis was most efficient in VLDL followed in descending order by IDL, HDL, and LDL. Even with hepatic lipase, phospholipid hydrolysis could not deplete VLDL and IDL of sufficient phospholipid molecules to account for the loss of surface phospholipid that accompanies triacylglycerol hydrolysis and decreasing core volume as LDL is formed (or for conversion of HDL2 to HDL3). Thus, shedding of whole phospholipid molecules, presumably in liposomal-like particles, must be a major mechanism for losing excess surface lipid as large lipoprotein particles are converted to smaller particles. Also, this shedding phenomenon, like phospholipid hydrolysis, is closely related to the hydrolysis of lipoprotein triacylglycerol.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1992

Interaction of size-fractionated heparins with lipoprotein lipase and hepatic lipase in the rat.

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.

Animals↗
PubMed1992

Release of lipoprotein lipase to plasma by triacylglycerol emulsions. Comparison to the effect of heparin.

It was previously known that lipoprotein lipase (LPL) activity in plasma rises after infusion of a fat emulsion. To explore the mechanism we have compared the release of LPL by emulsion to that by heparin. After bolus injections of a fat emulsion (Intralipid) to rats, plasma LPL activity gradually rose 5-fold to a maximum at 6-8 min. During the same time the concentration of injected triacylglycerols (TG) decreased by about half. Hence, the time-course for plasma LPL activity was quite different from that for plasma TG. The disappearance of injected 125I-labelled bovine LPL from circulation was retarded by emulsion. This effect was more marked 30 min than 3 min after injection of the emulsion. The data indicate that the release of LPL into plasma is not solely due to binding of the lipase to the emulsion particles as such, but involves metabolism of the particles. Emulsion increased the fraction of labelled LPL found in adipose tissue, heart and the red muscle studied, but had no significant effect on the fraction found in liver. The effects of emulsion were quite different from those of heparin, which caused an immediate release of the lipase to plasma, decreased uptake of LPL in most extrahepatic tissues by 60-95%, and increased the fraction taken up in the liver.

Animals↗
PubMed1992

Synthesis and transport of lipoprotein lipase in perfused guinea pig hearts.

Total lipoprotein lipase (LPL) activity did not differ significantly between hearts from fed or fasted guinea pigs. Incorporation of [35S]methionine into immunoprecipitable LPL was also the same. The rates at which perfused hearts from fed or fasted guinea pigs released LPL activity into the medium were, however, different (2 vs. 4 mU.g-1.min-1). These rates remained constant over 60 min of perfusion. Addition of heparin to the medium resulted in a peak of LPL activity during the first 2 min, followed by a shoulder of relatively high activity, which gradually declined to a constant rate from 30 min. The peak and shoulders were less with hearts from fed animals than with hearts from fasted animals, but the constant rates were similar. Cycloheximide added at the start of the perfusion had no effect on the peak or on the early part of the shoulder, but the LPL activity released from 30 min continuously decreased so that at 60 min it was less than half of that in controls. Studies in which the enzyme was pulse labeled by perfusion 15 min with medium containing [35S]methionine and then chased up to 75 min with unlabeled medium showed no differences in how LPL is transported and metabolized in hearts from fed vs. fasted guinea pigs. Thus the data suggest that factors outside the heart influence the disposition of heart LPL in vivo.

Animals↗
PubMed1992

Lipoprotein lipase enhances binding of lipoproteins to heparan sulfate on cell surfaces and extracellular matrix.

Lipoprotein lipase enhances binding at 4 degrees C of human plasma lipoproteins (chylomicrons, VLDL, intermediate density lipoprotein, LDL, and HDL3) to cultured fibroblasts and hepG-2 cells and to extracellular matrix. Heparinase treatment of cells and matrix reduces the lipoprotein lipase enhanced binding by 90-95%. Lipoprotein lipase causes only a minimal effect on the binding of lipoproteins to heparan sulfate deficient mutant Chinese hamster ovary cells while it promotes binding to wild type cells that is abolished after heparinase treatment. With 125I-LDL, lipoprotein lipase also enhances uptake and proteolytic degradation at 37 degrees C by normal human skin fibroblasts but has no effect in heparinase-treated normal cells or in LDL receptor-negative fibroblasts. These observations prove that lipoprotein lipase causes, predominantly, binding of lipoproteins to heparan sulfate at cell surfaces and in extracellular matrix rather than to receptors. This interaction brings the lipoproteins into close proximity with cell surfaces and may promote metabolic events that occur at the cell surface, including facilitated transfer to cellular receptors.

Animals↗
PubMed1992

Lipoprotein lipase in plasma after an oral fat load: relation to free fatty acids.

Lipoprotein lipase (LPL) releases fatty acids from triglyceride-rich lipoproteins for use in cellular metabolic reactions. How this hydrolysis, which occurs at the vascular endothelium, is regulated is poorly understood. A fatty acid feedback system has been proposed by which accumulation of fatty acids impedes LPL-catalyzed hydrolysis and dissociates the enzyme from its endothelial binding sites. We examined this hypothesis in humans who were subjected to an oral fat tolerance test of a mixed-meal type. Plasma triglycerides, free fatty acids, and LPL activity were measured before and repeatedly during a 12-h period after intake of the fat load. Since soybean oil with a high content of linoleic fatty acid was the source of triglycerides, a distinction could be made between endogenous free fatty acids (FFA) and FFA derived directly from lipolysis of postprandial triglyceride-rich lipoproteins. Mean LPL activity was almost doubled (P less than 0.01) 6 h after intake of the oral fat load. The rise in LPL activity was accompanied by an increase of plasma triglycerides and linoleic free fatty acids (18:2 FFA), but not of total plasma FFA, which instead displayed a heterogeneous pattern with essentially unchanged mean levels. The postprandial response of LPL activity largely paralleled the postprandial responses of 18:2 FFA and triglycerides. The highest degree of parallelism was seen between postprandial 18:2 FFA and LPL activity levels. Furthermore, the integrated response (area under the curve, AUC) for plasma measurements of LPL correlated with the AUC for 18:2 FFA (r = 0.40, P less than 0.05), but not with the AUC for plasma triglycerides (r = 0.21, ns). The high degree of parallelism and significant correlation between postprandial plasma LPL activity and 18:2 FFA support the hypothesis of fatty acid control of endothelial LPL during physiological conditions in humans.

Dietary Fats↗
PubMed1991

Lipoprotein lipases and vitellogenins in relation to the known three-dimensional structure of pancreatic lipase.

A 106-residue region of high similarity between lipoprotein/pancreatic/hepatic lipases and Drosophila vitellogenins encompasses four beta-strands with all residues but one strictly conserved or conservatively replaced between the structures, and enclosing the putative active site Ser-152. The properties suggest a common folding pattern but the region probably does not function as an 'interface recognition site' in the lipases, although it might well bind fatty acid esters of ecdysteroids or single lipid molecules in the vitellogenins. C-terminally of this 106-residue region, a surface loop ('flap') covers the active site. No residue within this loop is conserved through all lipases, but adjacent segments exhibit 60-70% residue identity. Hepatic and lipoprotein lipases probably hydrolyze both soluble and emulsified substrates at the same site. They lack residues corresponding to a second active site postulated in pancreatic lipase to account for hydrolysis of soluble substrates. In addition, due to structural differences the flap could prevent entry of soluble substrate molecules into the active site of pancreatic lipase.

Amino Acid Sequence↗
PubMed1991

Comparison of the action of lipoprotein lipase on triacylglycerols and phospholipids when presented in mixed liposomes or in emulsion droplets.

We have compared the action of lipoprotein lipase on liposomes of egg yolk phosphatidylcholine containing less than saturating amounts of trioleoylglycerol (less than 3%) and emulsion droplets of the same lipids. The amounts of the two types of lipid particles (expressed in terms of phosphatidylcholine) needed to reach substrate saturation of the enzyme were similar, indicating similar binding of the lipase to these two lipid/water interfaces. With liposomes, as opposed to emulsion droplets, albumin was not necessary for continued hydrolysis of triacylglycerols, presumably because product fatty acids could be accommodated in the phospholipid bilayer. The maximal rate of trioleoylglycerol hydrolysis was more than 10-fold higher, and the ratio of trioleoylglycerol/phosphatidylcholine hydrolysis was more than 50-fold higher with the emulsion droplets. Qualitatively similar results were obtained with hepatic lipase, and a lipase from Pseudomonas fluorescence. The data suggest that the lipases remained at the interface for several catalytic cycles, and that a continued supply of substrate molecules to the active site favored triacylglycerol entry from the core of the lipid particle, rather than sliding in from the side through lateral diffusion in the surface layer.

Apolipoprotein C-II↗
PubMed1991

Low-Mr heparin is as potent as conventional heparin in releasing lipoprotein lipase, but is less effective in preventing hepatic clearance of the enzyme.

This study compares a low-Mr heparin preparation with conventional heparin with respect to its interaction with lipoprotein lipase (LPL) in vitro and its effects on the enzyme in vivo. Both heparin preparations were polydisperse in binding to LPL, but on average the low-Mr preparation showed lower affinity. Thus both conventional and low-Mr heparin bound quantitatively to immobilized LPL, and were eluted as broad peaks when a salt gradient was applied, but the peak for low-Mr heparin was shifted towards lower salt concentrations. To displace LPL from immobilized heparin a higher concentration of low-Mr than of conventional heparin was needed. Injection of the low-Mr heparin into intact rats resulted in lower plasma LPL activity than did injection of an equal mass of conventional heparin, but when the liver was excluded from the circulation both heparin preparations resulted in similar plasma LPL activities. In perfused rat hearts, low-Mr heparin had at least the same effect on the release of LPL activity as did conventional heparin. In perfused livers, on the other hand, low-Mr heparin was less effective than conventional heparin in preventing the rapid uptake of exogenous labelled LPL. Hence the apparently lower average affinity of low-Mr heparin for LPL does not result in a demonstrably lower potency to release the enzyme from endothelial binding sites in peripheral tissues, but does result in a substantially decreased effect on the hepatic clearance of the enzyme.

Animals↗