P. Avogaro

ARE APOLIPOPROTEINS BETTER DISCRIMINATORS THAN LIPIDS FOR ATHEROSCLEROSIS

Plasma-levels of major lipids (cholesterol, triglyceride, high-density-lipoprotein cholesterol), two major apolipoproteins (apo-B and apo-A1), and two ratios (total-cholesterol/apo-B and apo-A1/apo-B) were studied in 218 survivors of myocardial infarction and 160 controls. Apolipoproteins were as good as lipids as discriminators between the populations under the age of 50 and better in the sixth to eighth decades.. Furthermore, values of total-cholesterol/apo-B and apo-A1/apo-B obtained from controls and normolipaemic survivors of myocardial infarction gave a bimodal distribution. The protein moiety of lipoproteins is a better discriminator than lipids between atherosclerotic subjects and controls.

Presence of a modified low density lipoprotein in humans.

Low density llpoproteins (LDL) collected from 18 fasting humans were subjected to ion exchange chromatography on DEAE Sepharose. By this procedure, a LDL subfraction was isolated with an electric charge more negative than the LDL bulk. This LDL appeared to be mainly characterized by low phospholipld content, high free cholesterol and protein content, low esterlfled/free cholesterol ratio, and a high content of conjugated dlenes, particularly of cholesterol esters. This subtraction, In an amount ranging from 5% to 20% of total LDL, was characterized by the presence of apo B-100 and protein aggregates that were reactive to anti-apo B monoclonal antibodies. Electron microscopy showed the more electronegative LDL to be heterogeneous in size with a tendency to aggregate. This LDL had low binding capacity with high affinity receptors of flbroblasts and low Immunoreactlvlty with the monoclonal antibodies that recognize the receptor binding domain of apo B. Finally, the Incubation of this LDL subtraction with cultured macrophages led to a higher Increase In cellular cholesterol In spite of a lower rate of uptake as compared to the LDL bulk and to acetyl-LDL. The more electronegative LDL subtraction that we Isolated for chemlcophyslcal behavior and conjugated dlene content may represent the peroxldized aliquot of human LDL.

Variations in apolipoproteins B and A, during the course of myocardial infarction

Abstract. The plasma apolipoproteins B and AI, and plasma lipids and lipoproteins, were studied in fifteen patients with acute myocardial infarction.

HDL-cholesterol, apolipoproteins A1 and B. Age and index body weight.

Some data of previous literature have emphasized a negative correlation between plasma apo A1, HDL cholesterol and coronary heart disease. The present paper stresses a high negative correlation existing both in females and males between values of index body weight (IBW) and plasma levels of HDL cholesterol and apo A1. No correlation has been found between age and, respectively, HDL cholesterol, apo A1 and apo B.

Total plasma apo E and high density lipoprotein Apo E in survivors of myocardial infarction

Total apo E in plasma and the amount of apo E-HDL were measured in 40 normolipidemic male survivors of myocardial infarction and in 40 controls. LDL-C, Lp(a) and apo B were significantly higher and HDL-C and apo A-I were significantly lower in survivors than in controls. Total plasma apo E did not differ between patients and controls, but HDL-E and the ratio HDL-E/apo A-I were lower in survivors. The data support the view that atherosclerotic patients are often characterized by abnormalities in the concentration and distribution of lipoproteins as well as of apoproteins, even in the presence of normal total plasma lipids.

Values of apo-AI and apo-B in humans according to age and sex

Abstract Two series of 100 subjects each, males and females, have been studied for the determination of plasma values of apo-AI, the major peptide of HDL, and of apo-B, the major peptide of LDL. To minimize a possible influence of variations in plasma lipid levels, two series of subjects were selected with very similar mean values of plasma cholesterol and triglyceride. Despite this criterion of selection apo-AI was significantly lower in males (127 ± 18 mg/l) than in females (137 ± 15 mg/l) while the reverse was true for apo-B (99 ± 16 mg/l in males vs. 91 ± 15 mg/l in females). Both apo-B and apo-AI showed a tendency to increase with advancing age with the greatest increase for apo-AI (in both sexes) and for apo-B (only in males) from the 3rd to the 4th decade of age.

Apoprotein B-48 is a constant finding in very low density lipoproteins of humans.

The results of this study indicate that very low density lipoprotein (VLDL) from the plasma of fasting normolipidemic or slightly hypertriglyceridemic subjects contains two apo B species. In SDS gel electrophoresis, the VLDL shows the presence of a major band corresponding to low density lipoprotein (LDL) apo B (apo B-100) and a minor band with the appropriate mobility of the lymph chylomicron apo B (apo B-48). The reactivity of monoclonal antibodies directed against opportunely selected human apo B suggests that the protein with the lower molecular weight corresponds to apo B-48. This finding was confirmed by using immunoadsorbants and affinity chromatography with monoclonal antibodies that react only with apo B-100. Through this method, VLDL were separated into two fractions: one that had only apo B-100 and one with both apo B-100 and apo B-48. Hepatic and intestinal VLDL may constitute different particles. The ratio of apo B-100 to apo B-48 in VLDL decreased as the mass of fasting plasma VLDL increased. This may improve our understanding of the metabolism of triglyceride-rich lipoproteins. The investigation of the new subspecies of apo B may be relevant in understanding the atherogenetic process and better defining the hyperlipidemic states.

Acute effects of L-carnitine on FFA and β-oh-butyrate in man

Summary L, Carnitine (1000 mg) was given intravenously to nine subjects by perfusion lasting four hours. Its effects on plasma levels of Cholesterol, Triglycerides, FFA and B-OH-B were recorded and compared with the effects in the same subjects of a saline solution infusion. Following L, Carnitine a significant drop of FFA was observed 60 minutes after starting infusion while a maximum was reached four hours later. B-OH-B rose significantly at 60′ reaching a plateau which remained unmodified up to the 4 th hour. No variations were observed in cholesterol and triglycerides plasma levels. The present data stress the view that Carnitine activates the carnitine acyltransferase system inducing an increased FFA oxidation and a consequential decrease of FFA plasma levels. At the same time, there is an increased production of ketone bodies and of their plasma levels. The shift of energy yielded by FFA oxidation from triglyceride synthesis to ketone body production may be a mechanism of a claimed lipid lowering effect of Carnitine.

Variations of plasma apoliporpoteins AI and B induced in liver patients by infusions of S-adenosyl-L-methionine

Summary 25 patients affected by liver cirrhosis, alcoholic or post-necrotic were included in the study. 15 out of them were given an infusion of S-adenosyl-L-methionine 250 mg in saline 500 ml for ten days; 10 patients received for the same time period 500 ml of saline enriched with g 1 of vitamin C. Before starting treatment and at the end plasma values of cholesterol, triglyce rides, apo-A I and apo-B were determined. In patients who received treatment with S-adenosyl-L-methionine values of apo-A I increased significantly while apo-B underwent a not significant decrease. In the controls no significant variations of the various examined parameters were observed.

Phospholipids in Human Atherosclerosis

Despite their relevant physiological and structural role, phospholipids (PL) have not gained favour in clinical assessment of human atherosclerosis. Already in 1951, Gertler et al. recorded higher values of serum lipid phosphorus in coronary patients than in controls. Furthermore, it was shown that the serum cholesterol/lipid phosphorus is increased in the presence of coronary heart disease (CHD). The same authors suggested a “chemotype” which included the analysis of serum cholesterol, phospholipids and uric acid. A recommandation was also given to increase the values of plasma PL, thus reestablishing a normal C/PL ratio. The meaning of the recorded variations of PL plasma values has not been discussed. An increased C/PL ratio has also been recorded in type II hyperlipoproteinaemia (Peeters 1976). Increased values of ratio sphyngomye-lin/phosphatidylcholine (SM/PC) was observed in types II and IIB, being normal in type IV (Peeters 1976). The lecithin/sphyngomyelin ratio is abnormally low in homozygotes with familial xanthomatosis hypercholesterolaemia (FXH) (Mills et al. 1976). In the low density lipoproteins (LDL) of FXH, an increased C/PL ratio was recorded with a decreased lecithin/sphyngomyelin ratio (Jadhav and Thompson 1979). Since this abnormal composition of LD1 normalizes following plasma exchange it has been suggested that the abnormal composition of LDL in FHX is due to hypocatabolism and then to the aging of LDL (Jashav and Thompson 1979). The chemical percentage composition of the major lipoprotein classes has been studied in survivors of myocardial infarction (Avogaro et al. 1979).