H.-J. Lisch

ESSENTIAL ROLE OF POST-HEPARIN LIPOPROTEIN LIPASE ACTIVITY AND OF PLASMA TESTOSTERONE IN CORONARY ARTERY DISEASE

89 consecutive men for whom coronary angiography was requested because of suspected coronary artery disease were investigated with respect to plasma lipids, lipoproteins, post-heparin lipoprotein lipase (LPL), and some hormones that influence LPL. The severity of coronary-artery disease was expressed by the coronary score (CS). Coronary-artery disease correlated with total plasma cholesterol, low-density lipoproteins, high-density lipoprotein cholesterol (HDL-chol), and HDL2. In addition, there was a strong negative correlation (r = -0.479, p less than 0.001) between CS and LPL, as well as positive correlations between CS and plasma triglycerides (p less than 0.01) and very low-density lipoproteins (VLDL, p less than 0.01). The impairment of LPL activity correlated with increased VLDL and decreased HDL-chol. The extent of coronary-artery disease is thus strongly influenced by an LPL deficit. LPL activity correlated with plasma testosterone, and there is evidence that low plasma testosterone may be partly responsible for the low LPL and HDL-chol.

Plasmalipoproteine bei Störungen der Schilddrüsenfunktion des Menschen

SummaryThe concentration of the main lipoprotein density classes and the postheparin lipolytic activity (PHLA) were determined in the plasma of 12 hyperthyroid and eight hypothroid patients in comparison with 12 euthyroid, metabolically healthy individuals. Low-density lipoproteins (LDL) and high-density lipoproteins2 (HDL2) were decreased in hyperthyreosis (p<0.01) and increased in hypothyreosis (p<0.01). No significant differences could be detected with respect to the concentration of very low-density lipoproteins (VLDL) as well as for HDL3, whereas intermediate-density lipoproteins (IDL) were higher in hypothyreotics than in controls (p<0.05). PHLA was increased in hyperthyreosis (p<0.01) and decreased in hypothyreosis (p<0.01). The chemical composition of LDL and HDL2 as well as the apolipoprotein composition of the protein moiety of HDL2 in hyperthyreosis and in hypothyreosis did not significantly differ from those in the control group. When data from all individuals studied were analyzed, no significant relationship could be detected between the concentrations of VLDL and HDL2, whereas HDL2 and PHLA correlated in a negative manner (p<0.05). It is suggested that HDL2, in addition to LDL, acts as carrier protein for the cholesterol increasingly yielded in hypothyreosis.ZusammenfassungDie Konzentration der Hauptlipoproteindichteklassen und die Post-heparin-lipolytische Aktivität (PHLA) wurden im Plasma von 12 hyperthyreoten und 8 hypothyreoten Patienten im Vergleich mit 12 euthyreoten, stoffwechselgesunden Kontrollpersonen bestimmt. Low-density-lipoproteins (LDL) und high-density lipoproteins2 (HDL2) waren bei Hyperthyreose erniedrigt (p<0,01) und bei Hypothyreose erhöht (p<0,01). Im Hinblick auf die Konzentration der very-low-density-lipoproteins (VLDL) und der HDL3 bestanden keine signifikanten Unterschiede, während die intermediate-density-lipoproteins (IDL) bei hypothyreoten Patienten erhöht waren (p<0,05). Die PHLA war bei Hyperthyreose erhöht (p<0,01) und bei Hypothyreose erniedrigt (p<0,01). Die chemische Zusammensetzung der LDL und HDL2 von Patienten mit Hyper- und Hypothyreose sowie die Apolipoproteinzusammensetzung des Proteinanteils der HDL2 unterschieden sich nicht signifikant von denen der Kontrollen. Bei Analyse der Daten aller untersuchten Individuen ergab sich keine signifikante Beziehung zwischen VLDL und HDL2, während HDL2 und PHLA signifikant negativ korrelierten (p<0,05). Es wird vermutet, daß HDL2 zusätzlich zu den LDL als Träger des bei der Hypothyreose vermehrt vorhandenen Cholesterins fungieren.The concentrations of the main lipoprotein density classes and the postheparin lipolytic activity (PHLA) were determined in the plasma of 12 hyperthyroid and eight hypothroid patients in comparison with 12 euthyroid, metabolically healthy individuals. Low-density lipoproteins (LDL) and high-density lipoproteins2 (HDL2) were decreased in hyperthyreosis (p less than 0.01) and increased in hypothyreosis (p less than 0.01). No significant differences could be detected with respect to the concentrations of very low-density lipoproteins (VLDL) as well as for HDL3, whereas intermediate-density lipoproteins (IDL) were higher in hypothyreotics than in controls (p less than 0.05). PHLA was increased in hyperthyreosis (p less than 0.01) and decreased in hypothyreosis (p less than 0.01). The chemical composition of LDL and HDL2 as well as the apolipoprotein composition of the protein moiety of HDL2 in hyperthyreosis and in hypothyreosis did not significantly differ from those in the control group. When data from all individuals studied were analyzed, no significant relationship could be detected between the concentrations of VLDL and HDL2, whereas HDL2 and PHLA correlated in a negative manner (p less than 0.05). It is suggested that HDL2, in addition to LDL, acts as carrier protein for the cholesterol increasingly yielded in hypothyreosis.

Post-heparin lipolytic activities and alterations of the chemical composition of high density lipoproteins in alcohol-induced type V hyperlipidemia.

In order to study the effects of chronic alcoholism, 3 groups of patients were investigated and compared to 10 healthy controls. Group I consisted of 9 heavy drinkers, who exhibited type V hyperlipidemia (HLP) under alcohol intake. Group II consisted of 7 patients, who previously had type V HLP under the influence of alcohol. At the time of the investigation, however, they had ceased alcohol drinking for at least 6 months and were normolipidemic. Group III consisted of 7 heavy drinkers without hyperlipidemia. Compared to controls, group I had significantly decreased plasma concentrations of high density lipoproteins2 (HDL2) and HDL3 (both P less than 0.01); activities of post-heparin lipoprotein lipase (LPL) and hepatic lipase (HTGL) as well were excessively decreased (both P less than 0.01). In group III LPL was also decreased (P less than 0.01), but HTGL was distinctly (P less than 0.01) higher than in controls. No such differences could be demonstrated for the patients of group II. Acute alcohol withdrawal from a patient suffering from alcoholism with HLP led to a sharp increase of LPL with a simultaneous decrease of VLDL within 2 days and a more delayed increase of LDL, HDL2 and HTGL, all reaching normal values within 12 days after cessation of alcohol drinking. With respect to the apolipoprotein (apo) composition of HDL2, patients of group I and group III exhibited a significantly lower percentual content of apo C-I at the expense of a significantly higher content of apo A-II as compared to controls and patients of group II. In group I and II, the percentual content of apo D in HDL2 was significantly higher than in controls and in group III. It is concluded that severe alcohol intake strongly impairs LPL in patients with HLP. The pronounced increase of HTGL in some patients (group III) may protect these individuals from HLP. The increased content of apo D in HDL2 may be a possible primary trait for alcohol-inducible HLP.

Lipoproteins, HDL-apolipoproteins, activities of hepatic lipase and lecithin-cholesterol acyltransferase in the plasma of patients with post-alcoholic end-stage liver cirrhosis

Summary12 patients with unequivocal post-alcoholic end-stage liver cirrhosis were compared with 12 healthy controls with regard to the plasma concentrations of lipids, lipoproteins (by rate zonal ultra-centrifugation) and apolipoproteins of high-density-lipoproteins (HDL) (by disc electrophoresis), as well as to the activities of lecithin-cholesterol acyltransferase (LCAT) in plasma and of hepatic lipase (HL) in post-heparin plasma. The cirrhotic group showed the following differences (all significant at thep<0.01 level) from the control group: Total cholesterol, HDL-cholesterol, very-low-density-lipoproteins (VLDL), HDL, and HL were decreased. Intermediate-density-lipoproteins (IDL) were not detectable in the cirrhotic group. Low-density-lipoproteins (LDL) did not differ significantly from controls. However, LDL from cirrhotic patients contained more triglycerides but less esterified and free cholesterol (allp<0.01). The percentage apolipoprotein composition of HDL did not differ significantly between controls and cirrhotics.Surprisingly, LCAT acivity in plasma as well as the ratios between esterified and free cholesterol in plasma, LDL, and HDL were nearly identical in both groups. It seems likely that LCAT activity decreases only in the states of acute or subacute liver injury or of biliary obstruction. Severe chronic liver damage as in our cases of end-stage liver cirrhosis without any signs of acute liver injury exhibits apparently no defect in cholesterol esterification.

[Relationship between the plasma concentration of the high density lipoproteins (HDL) and the intravenous fat tolerance in normo-and hypertriglyceridaemics].

The relationship between the plasma concentration of high-density-lipoprotein(HDL)-cholesterol, very-low-density-lipoprotein(VLDL)-triglycerides, and low-density-lipoprotein(LDL)-cholesterol and the fractional removal rate (K2) of an intravenously administered fat emulsion (Intralipid) was investigated in 13 normo- and 34 hypertriglyceridaemics. A highly significant correlation (p less than 0,001) between the plasma concentration of HDL-cholesterol and the fractional removal rate of exogenous triglycerides was found for both groups. No significant relationship existed between the concentration of VLDL-triglycerides and of LDL-cholesterol and the removal rate of exogenous triglycerides. These observations suggest a major role of HDL in the removal of plasma triglycerides.SummaryThe relationship between the plasma concentration of high-density-lipoprotein(HDL)-cholesterol, very-low-density-lipoprotein(VLDL)-triglycerides, and low-density-lipoprotein(LDL)-cholesterol and the fractional removal rate (K2) of an intravenously administered fat emulsion (Intralipid®) was investigated in 13 normo- and 34 hypertriglyceridaemics. A highly significant correlation (p<0,001) between the plasma concentration of HDL-cholesterol and the fractional removal rate of exogenous triglycerides was found for both groups. No significant relationship existed between the concentration of VLDL-triglycerides and of LDL-cholesterol and the removal rate of exogenous triglycerides.These observations suggest a major role of HDL in the removal of plasma triglycerides.ZusammenfassungBei 13 Normo- und 34 Hypertriglyzeridämikern wurden die Beziehungen zwischen den Plasmakonzentrationen von High-density-lipoprotein(HDL)-Cholesterin, Very-low-density(VLDL)-Triglyzeriden, Low-density-Lipoprotein(LDL)-Cholesterin und der fraktionellen Verschwinderate (K2) einer intravenös applizierten Fettemulsion (Intralipid®) untersucht. Für die Gruppe der Normal-personen und für die Gruppe der Hypertriglyzeridämiker bestand eine jeweils hochsignifikante Korrelation (p<0,001) zwischen der Plasmakonzentration von HDL-Cholesterin und dem K2-Wert. Zwischen der Plasmakonzentration der VLDL-Triglyzeride bzw. des LDL-Cholesterins und dem K2-Wert ergaben sich für beide Gruppen keine statistisch gesicherten Beziehungen.Auf Grund dieser Befunde dürften die HDL wesentlich am Abtrasport der Plasmatriglyzeride beteiligt sein.

Effect of treatment of the concentration of lipoproteins and the postheparin-lipolytic activity in the plasma of noninsulin-dependent diabetics.

SummaryTo study the effect of treatment on plasma lipid and lipoprotein concentration and on postheparin-lipolytic activity (PHLA) in plasma, 26 noninsulin-dependent diabetics were investigated who were treated with maximally effective doses of glibenclamide. The patients were randomly divided into two groups: In group I, glibenclamide was replaced by a long-acting insulin preparation given once daily at variable doses until satisfactory metabolic control was achieved. In group II, glibenclamide was replaced by placebo. At weeks 0, 1, 3, 7, and 12 after change of treatment, the following parameters were determined: Blood glucose, plasma concentrations of cholesterol, triglycerides, phospholipids, HDL cholesterol, very-low-density lipoproteins, intermediate-density lipoporteins, low density lipoproteins, high-density lipoproteins2 (HDL2), HDL3, and PHLA. At week 0, no statistically significant differences existed between group I and group II with respect to all parameters mentioned above. The replacement of glibenclamide by insulin resulted in a continous decrease of blood glucose (p<0.01) with a concomitant increase in HDL2 (p<0.01) and in PHLA (p<0.01) during the period of investigation. In contrast, replacement of glibenclamide by placebo exerted no significant influence on all determined parameters during 12 weeks. These data suggest that in noninsulin-dependent diabetics, who are inadequately controlled by sulfonylureas, an adequate insulin substitution is necessary to correct, apart from glucose metabolism, the impaired lipoprotein metabolism of diabetes mellitus. Sulfonylureas per se seem not to decrease the HDL2 fraction nor the PHLA.ZusammenfassungDie Wirkung der Behandlungsart des Diabetes auf die Lipide und Lipoproteine und auf die post-heparin-lipolytische Aktivität (PHLA) im Plasma von 26 insulinunabhängigen Diabetikern wurde untersucht. Die Patienten waren bisher mit einer maximal effektiven Dosis von Glibenclamid behandelt worden. Sie wurden in 2 randomisierte Gruppen unterteilt: In Gruppe I wurde Glibenclamid durch ein Insulindepotpräparat ersetzt. Insulin wurde einmal täglich verabreicht und die Dosis solange gesteigert, bis eine zufriedenstellende Einstellung erreicht war. In Gruppe II wurde Glibenclamid durch Placebo ersetzt. Zum Zeitpunkt der Wochen 0, 1, 3, 7 und 12 nach Umstellung der Therapie wurden folgende Parameter bestimmt: Blutglukose, die Plasmakonzentrationen von Cholesterin, Triglyzeriden, Phospholipiden, HDL-cholesterin, very-low-density-lipoproteins, intermediate-density-lipoproteins, low-density-lipoproteins, high-density-lipoproteins2 (HDL2), HDL3 und die PHLA. Zu Beginn der Studie bestanden keine signifikanten Unterschiede zwischen Gruppe I und II im Hinblick auf alle oben angeführten Parameter. Die Umstellung von Glibenclamid auf Insulin resultierte in einem ständigen Abfall der Blutglukose (p<0,01) bei gleichzeitigem Anstieg der HDL2 (p<0,01) und der PHLA (p<0,01) während des Untersuchungszeitraums. Im Gegensatz dazu hatte die Umstellung von Glibenclamid auf Placebo keinen signifikanten Effekt. Die Ergebnisse zeigen, daß bei insulinunabhängigen Diabetikern, die mit Sulphonylharnstoffpräparaten nicht mehr befriedigend eingestellt waren, eine Umstellung auf Insulin nicht nur zu einer weitgehenden Normalisierung des Glukosestoffwechsels sondern auch zu einer signifikanten Besserung der Störung im Lipoproteinstoffwechsel bei Diabetes mellitus führt. Glibenclamid per se dürfte weder die Konzentration der HDL2-fraktion noch die PHLA beeinflussen.

Effect of body weight changes on plasma lipids in patients with primary hyperlipoproteinemia

Summary In 30 untreated patients with type IIb, III, IV, and type V hyperlipoproteinemia plasma lipid concentrations were studied in relation to body weight over a period of up to 5 years. Significant intraindividual correlations were demonstrated between weight index and the logarithms to base 10 of the plasma triglyceride level in 2 of 3 type IIb patients, 2 of 3 type III patients, 8 of 13 type IV patients, and only 1 of 11 type V patients. These correlations were paralleled in about two thirds of the cases by correlations between weight index and the logarithm to base 10 of plasma cholesterol, and in approximately one half of the cases by correlations between weight index and the logarithm to base 10 of plasma phospholipid concentration, both of lower-grade significance. Total starvation led to a pronounced but transient reduction of all plasma lipid fractions, even in those patients without correlations between weight index and plasma lipids.

Initial cholesterol esterif ication rate in hyperlipoproteinaemia: effects of triglyceride-rich Iipoproteins

Abstract. The initial cholesterol esterification rate (LCAT activity) was determined in ninety‐four hyper‐lipidaemic subjects. LCAT activity was elevated in hypertriglyceridaemia, whereas patients with hyper‐cholesterolaemia had normal activities. In hypertri‐glyceridaemic subjects LCAT activity correlated with the concentrations of d 1.006 lipoproteins, plasma triglycerides, cholesterol and cholesterol esters and phospholipid levels. Addition of d < 1.006 lipoproteinto normal plasma resulted in a dose dependent stimulation of enzyme activity with a sigmoidal response curve. When the d < 1.006 lipoproteins were removed from hypertriglyceridaemic plasma by ultracentrifugation, the enzyme activity in the residual d > 1.006 fraction dropped, but still was higher than in normal plasma and correlated with the amount of d 1.006 lipoproteins originally present. Thus, high LCAT activity in hypertriglyceridaemia cannot be explained solely by the presence of an increased d < 1.006 lipoprotein concentration. An increase of enzyme concentration or changes in concentration or composition of other lipoproteins (high density lipoproteins) may contribute to the high LCAT activity in hypertriglyceridaemia.

Increased complexing of plasmatic lipids with fibrins in hyperlipoproteinaemias

Abstract Plasma was brought to coagulation by different reagents under differing conditions. The clots were then squeezed out and washed under standardized conditions and the lipid content of the resulting fibrins and the corresponding plasmas were analyzed. In hyperlipoproteinaemic patients the amount of plasmatic lipids complexed with fibrins was significantly greater than in normal subjects; and the percentage was greater in hypertriglyceridaemic patients. Increased amounts of lipids complexed with fibrins might inhibit fibrinolytic enzymes from reaching their substrate and therefore be partly responsible for the increased tendency to atherosclerosis and to thrombotic complications in hyperlipoproteinaemia. In normal subjects there was a positive correlation between plasma and fibrin triglycerides. No other correlations between lipid and coagulation parameters were observed.

Basale und Noradrenalin-(NA-)induzierte Lipolyse in isolierten Fettzellen des Menschen bei isocalorischer und hypocalorischer Diät

SummaryIn isolated human fat cells of the subcutaneous abdominal region the effect of noradrenalin on lipolysis was tested under isocaloric and hypealoric diet. It could be demonstrated that with hypocaloric diet, the basal lipolysis increased 4,5-fold and could not be further stimulated by maximal doses of noradrenalin. It is suggested that starvation results in a maximal activity of the hormone-sensitive lipase, which it is impossible to further increase by noradrenalin.ZusammenfassungAn isolierten Fettzellen des abdominellen Subcutanfettgewebes übergewichtiger Patienten unter isocalorischer und hypocalorischer Diät wurde die basale Lipolyse und deren Stimulierbarkeit durch Noradrenalin untersucht. Es konnte gezeigt werden, daß unter hypocalorischen Ernährungsbedingungen die basale Lipolyse auf das 4,5fache der Norm erhöht ist, und zum Unterschied von der Lipolyse unter isocalorischer Kost durch Noradrenalin nicht mehr signifikant gesteigert werden kann. Es ist anzunehmen, daß es im Hunger zu einer maximalen Aktivität der hormonsensitiven Lipase kommt, die durch maximale Dosen von Noradrenalin nicht mehr weiter stimuliert werden kann.