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Biomedical subjects

W C Hülsmann

Publications and source records attributed to W C Hülsmann.

At least 37 records · Page 2Linked to original sources
PubMed1989

Relationship between insulin-like growth factor-I and low-density lipoprotein cholesterol levels in primary hypothyroidism in women.

The effect of insulin-like growth factor-I (IGF-I) on the disturbance of lipid metabolism during primary hypothyroidism was studied in 12 women with primary hypothyroidism. Significant increases in both low-density lipoprotein (LDL) cholesterol and intermediate-density lipoprotein cholesterol were seen. Lipoprotein concentrations reverted to normal after substitution with thyroxine (T4) until the euthyroid state was reached. A decrease in IGF-I of 65% (P less than 0.005) was seen in hypothyroid patients and this was inversely correlated (r = -0.75; P less than 0.01) with the concentration of LDL cholesterol. Multivariate regression analysis of LDL cholesterol against IGF-I and free T4 showed that IGF-I determines the concentration of LDL cholesterol instead of free T4. Our data suggest that in hypothyroidism, IGF-I is a determinant of the concentration of LDL cholesterol. In addition, hypothyroidism can influence plasma lipoprotein metabolism by lowering the activity of the salt-resistant lipase (liver lipase).

Adolescent↗
PubMed1989

Endothelial lesions, dietary composition and lipid peroxidation.

The vascular endothelium can be regarded as a widely distributed organ with a pluripotent function in homeostasis and lipoprotein metabolism. There is now increasing evidence that the vascular endothelium is susceptible to oxygen radicals (oxidative stress). These radical molecules are capable of degrading the polyunsaturated acyl chains of membrane phospholipids (lipid peroxidation), hereby inducing pathologic changes in the underlying tissue. Since the fatty acid composition of our diet is reflected in the composition of cellular membranes, it is conceivable that their may be a relation between the dietary fatty acids and the tissue (endothelial) susceptibility towards lipid peroxidation. In addition, the occurrence of dietary antioxidant molecules (e.g., vitamin E) and trace elements (Se) may be important denominators of tissue protection against peroxidative processes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Cardiac lipoprotein lipase: effects of lipopolysaccharide and tumor necrosis factor.

Lipopolysaccharide (LPS), the active principle of certain endotoxins, protein-free perfused in rat hearts leads in 3 h to a considerable loss of lipoprotein lipase (LPL) activity. In the presence of albumin LPS has virtually no effect. Tumor necrosis factor (TNF) added instead of LPS had no effects on LPL activity during 3 h in vitro perfusion. LPS injected into rats intravenously leads within 3 h to severe toxic phenomena amongst which increased capillary permeability. This was visualized as increased rate of interstitial fluid formation in Langendorff hearts mounted 3 h after rats had been treated with LPS. LPL activity did not decline in 3 h lasting endotoxemia. Six hours after LPS injection, however, cardiac LPL activity was considerably lowered, although immunoblotting and immunohistochemistry still showed LPL protein to be present. These date indicate the presence of a considerable pool of inactive LPL protein in addition to active LPL, that can be released in the presence of heparin. The LPL activity is lowered by LPS injection after a lag phase of at least 3 h, while capillary endothelial cells are influenced more rapidly. The relatively late expression of TNF toxicity in cardiomyocytes of the intact heart is discussed.

Animals↗
PubMed1988

Effects of tumor necrosis factor (TNF) on lipolytic activities of rat heart.

Tumor Necrosis Factor (TNF) inhibits lipoprotein lipase activity in cultured myocytes and in the Langendorff rat heart after 3 h perfusion with TNF of glucocorticoid-pretreated rats. TNF acutely stimulates glyc(ogen)olysis and concomitantly endogenous lipolysis. The latter was significantly increased only when rats had been pretreated with glucocorticoid or fed a trierucate-rich diet. Under these conditions, contractile activity of the Langendorff hearts was acutely increased by TNF. The mechanism of the acute increase of contractile function and the accompanying increased glycolytic and lipolytic activities, by TNF, may be explained by increased cytosolic Ca2+ and cAMP levels.

Animals↗
PubMed1988

Aspects of fatty acid metabolism in vascular endothelial cells.

Long-chain fatty acids are an important source of energy in vascular endothelium. Their oxidation is stimulated by carnitine and inhibited by blockage of the mitochondrial respiratory chain. Excess fatty acid can be reversibly stored as triacylglycerol in the cells. Cultured vascular endothelial cells, in contrast to cardiac vascular endothelium in the intact heart, take up and intracellularly degrade artificial chylomicrons (intralipid enriched with apolipoprotein C-II) but not natural chylomicrons. Fatty acids not bound to albumin, such as those generated from chylomicrons in the lipoprotein lipase reaction, although initially a good source of substrate for beta-oxidation, endanger heart function. Fatty acid excess initiates the breakdown of the endothelial barrier between the vascular lumen and interstitium; it may precipitate edema formation, lead to insufficient oxygenation and finally cause loss of heart function.

Carnitine↗
PubMed1988

Effect of dietary fat composition on the metabolism of triacylglycerol-rich plasma lipoproteins in the postprandial phase in meal-fed rats.

Rats conditioned to eating fixed-size meals (meals at 7 AM and 7 PM), consuming diets rich in palm oil or sunflower seed oil, were used to study the metabolism of chylomicrons and hepatic very low density lipoproteins (VLDL) as a function of time after meal consumption. Rats fed a palm oil diet had higher serum triacylglycerol levels at 7 AM, before the meal (1.96 +/- 0.25 mM vs. 1.09 +/- 0.09 mM) and reached higher levels postprandially (4.32 +/- 0.48 mM vs. 2.87 +/- 0.18 mM) than sunflower seed oil-fed animals, due to higher levels of hepatic VLDL (at 7 AM) and higher levels of chylomicrons and hepatic VLDL (in the postprandial phase). These differences in serum triacylglycerol concentrations between the diets tested were found not to be due to differences in hepatic VLDL triacylglycerol secretion (similar rate for both dietary groups and not very much affected by meal consumption) or chylomicron triacylglycerol secretion (similar response profiles on both diets), pointing towards differences in plasma triacylglycerol catabolism. Subsequent double-label studies on triacylglycerol catabolism of chylomicrons from palm oil- and sunflower seed oil-fed animals in chow-fed recipients showed that palm oil triacyglycerol is catabolized slower than sunflower seed oil triacylglycerol. Furthermore, activities of postheparin plasma lipoprotein lipase tended to be higher in sunflower seed oil-fed animals. From these data we conclude that the relative hypertriglyceridemia found in palm oil-fed animals is due to less efficient catabolism and not to increased synthesis of plasma triacylglycerol.

Animals↗
PubMed1987

Structural modulation of salt-resistant rat-liver lipase alters the relative phospholipase and triacylglycerol hydrolase activities.

This paper demonstrates that structural modification of the heparin-releasable salt-resistant lipase of rat liver (liver lipase) alters its relative capacity to hydrolyze phospholipid and triacylglycerol emulsions. Enzymatic activities were modified by immunoinhibition and proteolysis and by selective amino acid agents. Binding of three different monoclonal antibodies resulted in a lower extent of inhibition of phospholipase than of triacylglycerol hydrolase activity. Degradation of the enzyme by trypsin under mild conditions led to a decrease of both enzyme activities in a different way. Triacylglycerol hydrolase activity was less affected than the phospholipase activity. Visualization of the proteolysis of the purified enzyme by immunoblotting revealed the actual breakdown of a 58 kDa protein into a 53 kDa protein band and subsequently in a 48 kDa one. Incubation of the purified enzyme by N-tosyl-L-phenylethylchloromethyl ketone (acting on cysteine or histidine) or N-ethylmaleimide (a sulfhydryl reagent) did not influence either enzyme activity. On the other hand, after the selective modification of lysine residue(s) by phenylisothiocyanate, the phospholipase A1 activity was stimulated by 68%, whereas the triacylglycerol hydrolase activity was completely lost. The role of a lysine residue(s) in the activity of the enzyme towards phospholipid and triacylglycerol emulsions is discussed.

Animals↗
PubMed1987

Substrates for energy metabolism in the heart: the role of the interstitial compartment.

Evidence is presented that, as in cardiomyocytes, vascular endothelial cells use fatty acids, in addition to glucose, as a respiratory fuel. Attention is focused on the cardiac interstitium, lined by vascular cells and cardiomyocytes, which may be enriched with metabolic products from these cells. Also, certain proteins are present in the interstitial fluid (Qi) such as plasma proteins and fatty acid binding protein (FABP). However, the concentration of FABP is so low in Qi that albumin is more important to shuttle long chain fatty acids in the interstitial fluid between cardiomyocytes and the vascular compartment. Under hypoxic conditions (hypo)xanthine, lactate and fatty acids may be expected to accumulate in the interstitium, as well as proteins from adjacent cells, such as xanthine oxidase from endothelial cells. This enzyme, acting upon the elevated level of (hypo)xanthine, giving rise to O2-., may be involved in the damage of the ischaemic heart. The significance of the interstitium in ischaemia and in fibrosis following long standing cardiac lipidosis is briefly discussed, as well as the possible mechanisms involved in fatty acid transport in the heart.

Animals↗
PubMed1987

Dietary fatty acids and myocardial function.

It is widely recognized that dietary polyunsaturated fatty acids (PUFA's) and cholesterol can profoundly influence the development of atherosclerotic plaques in coronary vessels, which may lead to myocardial infarction. The possibility that dietary fatty acids may also directly influence cardiac function has received less attention. We therefore reviewed the evidence of the effects of dietary fatty acids, in particular n-3 and n-6 PUFA's, on myocardial phospholipid fatty acid composition and cardiovascular performance. Heart organelles appear to incorporate uncommon fatty acids like 22:1 and trans- 18:1. Diets enriched with 22:1 induce myocardial lipidosis. N-9, n-6 and n-3 families compete among membrane C20 and C22 acids. Several studies have dealt with the relation between diet-induced changes of cardiac membrane (sarcolemma, sarcoplasmic reticulum and mitochondria) phospholipids and membrane function. In view of the variety of diets used and of the membrane functions studied, the results do not permit equivocal interpretation. Several investigators have reported an altered stress response of the heart due to a change of PUFA's in the diet. In rats fed with a low 18:2n-6/18:3n-3 ratio combined with relatively low amounts of saturated fatty acids, a high incidence of myocardial lesions has been observed. Pigs are less sensitive but more susceptible to the development of vitamin E deficiency, when the dietary PUFA content is high. Increased contractility and coronary flow rate have been reported for Langendorff-perfused hearts of rats fed 18:2n-6-rich diets. The effects on coronary flow rate are possibly related to alterations in eicosanoid synthesis, which may also contribute to the reduction by n-6 or n-3 PUFA's in infarct size, magnitude of recovery of function and suppression of reperfusion arrhythmias following release of a coronary artery ligation. On the other hand, increased peroxidation of membrane lipids, due to their high content of n-3 PUFA, may be deleterious.

Animals↗
PubMed1987

Synthesis, storage and degradation of myocardial triglycerides.

In the mammalian myocardium, an active triglyceride synthesis pathway is operating, (re)esterifying activated fatty acids from endogenous or exogenous sources, with the glycolytically derived three-carbon intermediates dihydroxyacetone-phosphate and glycerol-3-phosphate by the so-called Kennedy pathway. The seven enzymes of triglyceride synthesis are membrane bound and located at the sarcoplasmic reticulum. The first enzyme in the glycerol-3-phosphate pathway, glycerol-3-phosphate acyltransferase, is proposed to be rate limiting for triglyceride formation. This microsomal enzyme is regulated by phosphorylation (inactiycation)-dephosphorylation (activation) coupled to the beta-receptor--adenyl cyclase--protein kinase system. Additional regulatory steps in triglyceride formation are the reactions catalyzed by the microsomal phosphatidic acid phosphatase and diglyceride acyltransferase. Intracellular triglycerides occur as free floating cytosolic droplets, membrane-bound particles and lipid-filled lysosomes. No consensus exists about the metabolically active portion of myocardial triglycerides. Various lipases have been proposed to be involved in endogenous lipolysis: the lysosomal acid, microsomal and soluble neutral triglyceride, intracellular lipoprotein lipases and the microsomal di- and monoglyceridase. It has been acknowledged that the bulk of the intracellular neutral lipase represents the precursor of vascular lipoprotein lipase. The presence of a neutral lipase, as distinct from lipoprotein lipase, in the rat heart was recently advocated. Endogenous lipolysis is a hormone-sensitive process. Hormone-sensitivity may involve direct alteration of enzyme activity by protein phosphorylation-dephosphorylation but is also dependent on the removal rate of product fatty acids, since feedback inhibition is a common property of all lipases in the heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Stimulation of myocardial neutral triglyceride lipase activity by adenosine-3':5'-monophosphate: involvement of glycogenolysis.

Endogenous lipolysis can be influenced by various hormones. Hormonal stimulation of endogenous lipolysis in the Langendorff heart was diminished by inhibition of glycogenolysis. Therefore we studied the influence of glycogenolysis on the cAMP-dependent activation of the neutral triglyceride lipase activity using a 40,000 X g post mitochondrial supernatant fraction from rat heart homogenates. In the presence of cAMP and ATP neutral triglyceride lipase activity was stimulated by 40%. This stimulation could not be detected in supernatants from which glycogen was removed after incubation in the presence of amyloglucosidase. Addition of glycogen overcomes this loss of stimulation. The activation of neutral triglyceride lipase by cAMP and ATP was mimicked by glucose plus ATP as well as by glycerol-3-phosphate but not by glyceraldehyde-3-phosphate. Moreover, the cAMP stimulation of neutral triglyceride lipase activity was suppressed by low amounts of palmitoyl-CoA indicating product inhibition of lipase activity. These results indicate that the level of intracellular precursors of fatty acid re-esterification, by determining the removal rate of product fatty acids, may be the major determinant of the stimulation of lipolysis by cAMP.

Animals↗
PubMed1987

Cholesteryl esterase activities in ventricles, isolated heart cells and aorta of the rat.

Cholesteryl esterase activities were determined in homogenates of rat heart (ventricles), isolated, calcium-tolerant, cardiac myocytes and aortic tissue and were compared with acid and neutral triglyceride lipase activities in these fractions. Using cholesteryl oleate/phosphatidylcholine/taurocholate emulsions and digitonin pretreatment of the enzyme fractions, acid and neutral cholesteryl esterase activities were measured in all tissue preparations. In contrast to the acid and neutral triglyceridase and acid cholesteryl esterase activity, the neutral cholesteryl esterase activity was subject to substrate inhibition. Upon isolation of cardiac myocytes, and in contrast with the recovery of neutral triglyceride lipase activity, only a small portion of the neutral cholesteryl esterase (6%) was recovered, suggesting that nonmyocyte neutral cholesteryl esterase activity markedly contributes to the relatively high activity detectable in whole ventricular homogenates. The recovery of large amounts of neutral cholesteryl esterase activity in the supernatant of collagenase-digested heart tissue, obtained during the isolation of myocytes, which is also markedly enriched in activities of two endothelial marker enzymes (5'-nucleotidase and angiotensine-converting enzyme) may indicate the predominant contribution of neutral cholesteryl esterase activity from coronary endothelial cells to this activity detectable in ventricular homogenates. Relative to the activity in ventricular and myocyte homogenates, aorta homogenates possessed the highest specific neutral cholesteryl esterase activity. We propose that in addition to coronary endothelium, smooth muscle cells also contribute to the neutral cholesteryl esterase activity in ventricular homogenates.(ABSTRACT TRUNCATED AT 250 WORDS)

5'-Nucleotidase↗
PubMed1987

Comparison of mackerel-oil and lard-fat enriched diets on plasma lipids, cardiac membrane phospholipids, cardiovascular performance, and morphology in young pigs.

Purified mackerel-oil extract or lard fat (9.1% wt/wt) was added to a basal diet of young pigs for 8 wk. Effects on plasma lipids, glucose and insulin, cardiac membrane phospholipids, cardiovascular performance, and morphology were studied. A time-dependent reduction of plasma triglyceride (62%), total cholesterol (41%), and HDL cholesterol (47%) was found in the mackerel-oil-fed pigs. The postprandial glucose and insulin response may indicate a mackerel-oil-induced resistance of insulin receptors. Although the polyunsaturated fatty acid composition of cardiac sarcolemma widely differed between the two groups, all determined indices of heart function were equal. It is concluded that consumption of a fish-oil diet with a low content of monoenes and supplemented with antioxidants reduces plasma lipid levels without producing pathological side effects.

Animals↗
PubMed1987

On the possible role of long chain fatty acylcarnitine accumulation in producing functional and calcium permeability changes in membranes during myocardial ischaemia.

A radioisotope procedure was used to determine long chain fatty acylcarnitine concentrations in fractions of porcine myocardium that had been subjected to different periods of ischaemia (0, 1, 2, and 3 h). In myocardial tissue from non-ligated hearts acylcarnitine concentrations were 0.32(0.03) and 1.53(0.04) nmol.mg-1 protein for homogenate and sarcolemma enriched membrane respectively, which indicates a preferential membrane localisation of long chain fatty acylcarnitine. Both the total and membrane acylcarnitine contents were increased about twofold after 2 h of ischaemia. The accumulation of long chain fatty acylcarnitine was not correlated temporally with changes in adenosine triphosphate dependent calcium uptake activity of homogenates (mainly a function of sarcoplasmic reticulum membranes), sodium gradient induced calcium uptake, and calcium permeability of sarcolemma preparations. Homogenate adenosine triphosphate dependent calcium uptake was decreased by 36% after 3 h of ischaemia. Sodium gradient induced calcium uptake was enhanced about twofold after 1 h of ischaemia, and calcium permeability of sarcolemmal vesicles was decreased by 20% after 3 h of ischaemia. After in vitro incubation of isolated sarcolemma membranes with (1-14C)-palmitoylcarnitine radiolabelled molecules that remained associated with the membrane even after repeated washing were incorporated. No changes were observed in the sodium gradient induced calcium uptake when less than 6 nmol (1(-14)C)- palmitoylcarnitine per mg sarcolemma protein were bound or incorporated into the lipid phase. This exceeded the maximal endogenous concentrations of 3.2(0.6) nmol long chain fatty acylcarnitine per mg sarcolemma protein observed during myocardial ischaemia. The results suggest that the intracellular increase in long chain acylcarnitine during almost zero myocardial flow is not critical to sarcolemmal sodium and calcium permeability and sarcoplasmic reticulum calcium pumping activity.

Acetylcarnitine↗
PubMed1987

Early damage of vascular endothelium during cardiac ischaemia.

To determine the site of reperfusion damage after ischaemia the leakage of xanthine dehydrogenase and xanthine oxidase was assessed in vascular and interstitial effluents. Contractile function was reduced during hypoperfusion but improved after the addition of superoxide dismutase and vasoxin to the perfusion medium. Both interstitial fluid and coronary effluent showed dehydrogenase and oxidase activity after no flow ischaemia. Furthermore, the ratio of lactate dehydrogenase to creatine kinase in coronary effluents was reduced. These findings indicate that the myocardial interstitium may be a site of ischaemic membrane damage since this space contains hypoxanthine and xanthine oxidase. The protective effect of superoxide dismustase also indicates the possibility of damage due to oxygen derived radicals in the cardiac interstitium during low flow perfusion.

Adrenergic alpha-Agonists↗
PubMed1986

Monoclonal antibodies against salt-resistant rat liver lipase. Cross-reactivity with lipases from rat adrenals and ovaries.

To obtain monoclonal antibodies against rat salt-resistant liver lipase, mice were immunized with enzyme purified from heparin-containing rat liver perfusates. Hybridomas were screened for antibody production by means of an enzyme-linked immunosorbent assay (ELISA) and an immunoprecipitation assay. Five hybridoma cell lines secreting antibodies against rat liver lipase indicated as A, B, C, D and E, have been obtained. All antibodies possess gamma one (gamma 1) heavy chains and kappa (kappa) light chains. The antibodies precipitate salt-resistant lipase from rat post-heparin plasma, are positive in ELISA, inhibit liver lipase activity and bind monospecifically with the enzyme as shown by immunoblotting. The monoclonal antibodies showed no significant reactivity with human liver lipase. The salt-resistant lipases of rat adrenals and ovaries are also precipitated by the monoclonal antibodies directed against the liver enzyme. Therefore, the heparin-releasable lipases of the liver, adrenals and ovaries possess identical epitopes.

Adrenal Glands↗