Serum magnesium, copper and zinc concentration changes in lower limb ischemia and postoperative treatment.

A prolonged state of ischemia of the lower limbs may affect the balance of some metal ion concentrations in blood. Ischemia of a critical degree, surgery and complicated postoperative periods invoke an inflammatory response, increased production of interleukin-6 (IL-6) and acute phase proteins (APhP) as a response to tissue destruction. The aim of the present study was to investigate the modification of Mg, Cu and Zn concentrations in the serum of patients with atherosclerosis obliterans (AO) before surgery and during the postoperative treatment, and the effect of chronic ischemia of the lower limbs on the relationship between the elements. The group studied consisted of 54 men with chronic ischemia of the lower limbs due to AO. The mean value of serum Mg concentration in men with AO was found to be significantly lower, and that of Cu to be higher, in comparison with the control group. In critical ischemia, the mean serum Cu concentration and the ratio Cu/Zn were found higher than in moderate ischemia. The postoperative treatment results in changes in Cu and Zn concentrations in the AO group that are inversely related to the levels before surgery.

Effect of simvastatin on trioleylglycerol hydrolysis and transacylation with cholesterol in serum of outpatients with coronary heart disease.

At present, the most effective drugs in treating hypercholesterolemia and atherosclerosis are the statins, which are potent inhibitors of the rate-limiting enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Serum triacylglycerol (TAG) levels associate positively with the risk for coronary heart disease (CHD). Triacylglycerols are mainly hydrolyzed by the enzyme lipase (glycerol ester hydrolase [GEH], EC 3.1.1.3) but can also be transformed by transacylation with cholesterol (glycerol ester:cholesterol acyltransferase [GECAT], EC 2.3.1.43). We evaluated the effect of a 3-month treatment with simvastatin (10 mg/day) on GEH and GECAT activity in the serum of 26 outpatients with CHD. The activity of both GEH and GECAT was reduced in the CHD group compared with that in the control group: 5.9 +/- 0.9 mU/mg vs. 7.5 +/- 1.8 mU/mg and 11.1 +/- 1.4 mU/mg vs. 19.3 +/- 3.3 mU/mg, respectively (p < or = 0.05). In addition to the well known effect of reducing total cholesterol and low-density lipoprotein cholesterol in patients with CHD, we observed two other results of simvastatin treatment. First, GEH activity increased to values similar to those found in healthy subjects and, simultaneously, GECAT activity decreased. Trioleylglycerol transacylation with cholesterol amounted to 72% and hydrolysis to 28% in the control group and to 65% and 35% in the CHD group, respectively. After simvastatin treatment, transacylation with cholesterol and hydrolysis amounted to 51% and 49%, respectively. In conclusion, by increasing GEH and reducing GECAT, simvastatin seems not only to affect cholesterol synthesis but also to alter triacylglycerol metabolism. Further studies are needed to determine the physiological significance of these changes and their relationship with the development of atherosclerosis.

The activity of cholesterol esterase and ceruloplasmin are inversely related in the serum of men with atherosclerosis obliterans.

BACKGROUND: Ceruloplasmin is a copper-containing (2-glycoprotein and a member of the acute phase reactant family. Parallel changes in ceruloplasmin and copper concentration have been observed in diseases accompanied by severe inflammation, indicating a closely related process. Cholesterol esterase participates in lipoprotein degradation by the hydrolysis of cholesteryl esters in low density lipoproteins (LDL-CE). LDL-CEs are substrates for cholesterol esterase, but can also undergo oxidation by metal ions. The reduction of lipid hydroperoxides has been claimed to play a key role in the control of lipid peroxidation in living systems. MATERIAL AND METHODS: The experimental group consisted of 16 men with atherosclerosis obliterans of the lower limbs, with 12 healthy male volunteers as a control group. The activity of cholesterol esterase (CEase), ceruloplasmin (Cp), and glutathione peroxidase (GPx), and the concentrations of malonyldialdehyde (MDA) and copper were determined in serum samples. RESULTS: CEase and Cp activity and copper concentrations were found to be greater in the AO group than in the controls. In addition, CEase and Cp were negatively correlated (r=(0.65, p< or = 0.05) in the serum of men with AO, but not in the controls. Moreover, copper concentration was significantly correlated with the activity of Cp and GPx (r=0.81 and r=0.58, respectively). The reduced GPx activity and the higher MDA concentration found in the AO group indicate a decline in the antioxidative barrier of plasma. CONCLUSIONS: The results reported here show an inverse relationship between the activities of CEase and Cp in chronic arterial occlusion of the lower limbs, which may reveal the interaction between the antioxidant and lipolytic enzymes.

The influence of simvastatin on lipase and cholesterol esterase activity in the serum of men with coronary heart disease.

Several studies have demonstrated that any beneficial effects of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins), of which simvastatin (Merck Sharp & Dohme) is an example, on coronary events are linked to their hypocholesterolemic properties. The in vivo effects of simvastatin treatment on lipase (GEH = glycerol ester hydrolase) and cholesterol esterase (CEase) activity in the serum of men with coronary heart disease (CHD) were examined. GEH and CEase activity in the serum of men with CHD, before simvastatin treatment, was lower than in the control subjects. In our study we have provided evidence that simvastatin increases GEH activity in a time-dependent manner, but has no effect on CEase activity. This suggests that simvastatin can directly affect acylglycerol metabolism by an increase in GEH activity and may therefore be suitable for the treatment of combined lipoprotein disorders characterized by elevation of triacylglycerols.

Prostaglandin E1 influences serum cholesterol esterase and lipase activity in different ways.

The in vitro and in vivo effects of prostaglandin E1 on cholesterol ester hydrolase (CEase) and lipase [glycerol ester hydrolase (GEH)] activity in human serum were examined. Cholesterol esterase and lipase activity in the sera of men with atherosclerosis differed substantially from that in the control subjects. CEase activity was raised and GEH activity suppressed in the serum of men with atherosclerosis compared with controls. Prostaglandin E1 in vitro was found to suppress lipase but to increase cholesterol esterase activity to some extent. However, in vivo activities of GEH and CEase in the sera of men with chronic arterial occlusions of the lower limbs treated with prostaglandin E1 revealed that lipase activity was increased but that cholesterol esterase activity was unchanged. Recent studies have demonstrated that by altering the metabolic pathways of acylcholesterols and triacylglycerols, prostaglandin E1 may lead to the development of new strategies for retarding atherosclerosis.

Serum glycerol ester hydrolase activity is related to zinc and copper concentrations in atherosclerosis obliterans and aneurysm.

Although the body status of zinc and copper in cardiovascular disease (CVD) has been shown to be important little is known about the effect of these trace element alterations on lipolytic enzyme activities in atherosclerosis human subjects. The aim of the present study was to evaluate the multiple relationships between lipase (GEH = glycerol ester hydrolase, EC 3.1.1.3) activity, zinc, copper and lipid concentrations in serum and the arterial wall of men with atherosclerosis obliterans (AO) and abdominal aortic aneurysm (AA). The mean concentrations of zinc and copper in serum were found to be higher in AO in comparison to AA. Low but significant correlation coefficients for zinc and lipase catalytic activity (r > or = 0.64) and lipase metabolic activity GEH/TAG (r > or = 0.67) were calculated in serum in AA. Multiple correlation coefficients (R) for three variables GEH-Zn-Cu were found to be significant for both AO and AA (R > or = 0.45 and 0.68, respectively) in serum but not in the arterial wall. Multiple relations for GEH/TAG-HDL-C (LDLC)-Zn(Cu) were found to be significant (R > or = 0.63) in serum in AA. The results indicate the influence of zinc and copper on the activity of lipase and lipid concentrations and suggest that the multiple relations may provide a better understanding of the role these elements play in atherosclerosis than relations between 2 substances.

[Function of platelets in patients with occlusive atherosclerotic arterial disease of the lower extremities]. / Czynnosc krwinek plytkowych u chorych na miazdzycowe niedokrwienie konczyn dolnych.

The platelet function as well as parameters of lipid metabolism and glucose tolerance were investigated in 30 men with occlusive atherosclerotic arterial disease of the low extremities (IIIB or IV Fontaine's stage). The platelet aggregation, platelet survival, activity of intraplatelet metabolism of arachidonic acid, radiofibrinogen binding to platelet, circulating platelet aggregates and both the activity of factor VIII and the concentration of von Willebrand factor antigen in the plasma were measured. In the majority of patients the impairment of platelet aggregation with ADP, enhancement of radiofibrinogen binding to platelets and an increase of factor VIII level in the plasma were established. There was an interrelationship between platelet dysfunction and disturbances of lipid metabolism. Platelet survival was shortened in patients with moderate hyperlipidemia and correlated with a concentration of HDL-cholesterol in the serum. The radiofibrinogen binding to platelets was the most pronounced in patients with severe hyperlipidemia and correlated with a concentration of total cholesterol in the serum. The results may suggest the potential usefulness of antiplatelet drugs in patients with occlusive atherosclerotic arterial disease.

The substrate specificity of glycerol ester hydrolase from pig aorta and serum.

The activity of glycerol ester hydrolase (GEH) from aorta wall, at optimum pH and triacylglycerol substrate concentration (optimal for each substrate) decreased in the following order: C18:1 greater than or equal to C18:2 greater than or equal to C18:0 greater than or equal to C18:3 greater than or equal to C16:0. At optimum pH and the same substrate concentration (1 mM), the activity of GEH from aorta wall decreased in a slightly different order: C18:1 greater than or equal to C18:2 greater than or equal to C18:3 greater than C18:0 greater than C16:0 and that of the enzyme from serum in the order: C18:1 = C18:3 greater than C18:2 greater than or equal to C16:0 greater than or equal to C18:0. These differences in substrate affinity of GEH may influence the metabolism and accumulation of acylalcohols and alcohols in arterial wall and serum.

Oleylglycerol hydrolysis and acyl-CoA-independent transacylation with cholesterol by enzyme preparations from pig aorta.

We demonstrated preferential hydrolysis of trioleylglycerol greater than 1.3-dioleylglycerol greater than 1-monooleylglycerol expressed as acyl equivalents of glycerol rather than fatty acid released by pig aortic lipase. Transacylation with cholesterol occurred in the reverse order of the substrates in an appropriate reaction system. The pathobiochemical importance of the results with respect to metabolism and differential accumulation of acylglycerols and acylcholesterols in the arterial wall is discussed.

Effects of substrate fatty acids on products of lecithin hydrolysis and acyl-CoA-independent transacylation with cholesterol by aortic enzyme preparations.

The acyl composition of substrates and products of enzymatic hydrolysis and transacylation of lecithin with cholesterol in the arterial wall was investigated. Saturated acyl residues predominated in lysolecithin and unsaturated ones in acids released by hydrolysis of egg lecithin. In the reaction system with cholesterol, saturated acyls predominated in both lysolecithin and acids released whereas unsaturated ones were more abundant in newly formed acylcholesterols. Mainly unsaturated acyls were present in the hydrolysis products from soybean lecithin in the reaction systems with and without cholesterol. For acylcholesterols formed in the presence of either lecithin, the percent values are in the numerical order of C18:2 greater than C18:1 greater than C16:0 greater than or equal to C18:0. It It is concluded that acyl preferences and interactions in the enzyme-catalyzed reactions studied may contribute to the different accumulation and removal of the compounds involved from the artery.

Cholesterol ester degradation by transacylation with lysolecithin and hydrolysis in the arterial wall.

Transacylation with lysolecithin of cholesterol oleate > linolenate > linoleate > palmitate > stearate, along with different hydrolysis of these esters, and acyl transfer from lecithin on cholesterol in appropriate two-substrate reactions mixtures with enzyme extract from pig aorta and cofactors, have been demonstrated. The results are discussed according to the acylenzyme theory of substrate decomposition and in relation to the metabolism of lipids in the arterial wall.

Cholesterol ester:lysolecithin transacylation in the aorta.

Acyl transfer from cholesteryl oleate on lysolecithin to release cholesterol and form lecithin has been demonstrated in the aortic wall. Mechanism of the enzyme-catalyzed transacylation is considered in relation to the arterial cholesterol ester hydrolase.

Effect of substrate composition and concentration on aortic cholesterol ester hydrolase activity.

Cholesterol ester hydrolase activity of pig aorta has been examined under optimum experimental conditions for hydrolysis of different cholesterol esters. The enzyme specific activity values were in the numerical order of substrates hydrolyzed: cholesteryl linoleate larger than or equal to linolenate greater than palmitate larger than or equal to stearate greater than oleate. The results are discussed in relation to the arterial accumulation of cholesterol esters.