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ABSTRACT. We characterized the lipid-lipoprotein abnormalities encountered in a series of 45 nonnephrotic uremic children with various degrees of chronic renal insufficiency. A mild hypertriglyceridemia associated with decreased serum high-density lipoprotein cholesterol levels was confirmed. The correlation between high-density lipoprotein cholesterol and creatinine clearance showed a power behavior with a marked decrease in high-density lipoprotein cholesterol below a creatinine clearance value of 40 ml/min/1.73 m2. A number of uremic children accumulate an abnormal population of very low-density lipoprotein particles in their plasma. On agarose gel electrophoresis these particles migrate as a slow moving pre-j3 band and are clearly distinguished from the regular fast moving pre-8 very low-density lipoprotein band. This electrophoretic phenomenon has been called double pre-j3 lipoproteinemia. The prevalence of double pre-j3 lipoproteinemia increased significantly with the degree of impairment of renal function, reaching highest figures in patients on hemodialysis. Accordingly, the very low-density lipoprotein cholesterol/triglyceride ratio also was significantly increased. The double pre-j3 lipoproteinemia phenomenon was not detected in any of the control, nonuremic subjects. The clinical importance of double pre-j3 lipoproteinemia in uremic plasma is related to its possible atherogenic role. (Pediatr Res 21: 462-465,1987) Abbreviations DPBL, double pre-j3 lipoproteinemia VLDL, very low-density lipoproteins HDL-CH, high-density lipoprotein cholesterol AGE, agarose gel electrophoresis

Summary: A total of 42 family members, 21 females aiid 21 males, distributed in 3 generations were studied; 32 were blood related while 10 wefe eontrols (not blood-related).The familial propositus, a young male subject 36 years oldj who had suffered from juvenile acute myocardial infarction, exhibited uppn lipoprotein agarose gel electrophoresis two distinct pre-beta bands. The slow prebeta component turned out to be a "sinking pre-beta", the Lp(a) lipoprotein. The familial distribution of the character "sinking pre-beta lipoprotein", äs it appeared on agarose gel electrophoresis of whole serum, and the segregation analysis data coiafirm an autosomal dominant transmission.No sex differeiices were observed in the prevalence of the sinking pre-beta lipoprotein. Serum mean levels of total cholesterol, triglycerides, apolipoprotein A-I and B and of the very low density total cholesterol/triglycerides ratio did not discriminate between (4-) and (-) "sinking pre-beta lipoprotein". In all the family jnembers the Lp(a) antigen was measüred by rocket immunoelectrophoresis.Comparing the Lp(a) values with the behaviour of the "sinking pre-beta lipoprotein" in agarose gel electrophoresis, we demonstrated that the ability to visualize a slow moving pre-beta component, identified äs the "sinking pfe«beta lipoprotein", is correlated with serum Lp(a) levels above 0.3 g/l.An inverse relationship between apolipoprotein A-I and Lp(a) values was observed (r = 0.36; p < 0.05). In spite of relatively löw apolipoprotein A-I levels and high Lp(a) values, no clinical patterns of atherosclerotic diseases were found in the family inembers. The reasons for this discrepancy are discussed. Pagnan, Kostner, Braggion, Ziron, Bittolo Bon and Avogaro: Familial study on "sinking pre-beta lipoprotein" Familien-Studie über "sinking prae-beta", das Lp(a)-Lipoprotein und seine Beziehungen zu Serumlipiden, Apolipoprotein A-l und B sowie klinisch manifester ArterioskleroseZusammenfassung: Aus drei Generationen wurden insgesamt 42 Familienangehörige, 21 männlich und 21 weiblich, untersucht; davon waren 32 blutsverwandt, während 10 nicht-blutsverwandte als Kontrollen dienten.• r Der vorgestellte Fall, ein 36jähriger M'ann, der an jugendlichem akuten Myokardinfarkt erkrankte, zeigte in der Lipoprotein-Agarosegelelektrophorese zwei deutlich unterschiedene prae-ß-Banden. Die längsame prae-ß-Komponente erweist sich als ein "sinking prae-ß", das Lp(a)-Lipoprotein.Die familiäre Verteilung des Charakteristiküms "sinking pfae-ß"-Lipoprotein, nachgewiesen durch Agargelelektrophorese des Gesamt-Serums, und die Daten der Aufspaltungsanalyse bestätigen eine autosomal dominante Vererbung.In der Prävalenz des "sinking prae-ß"-Lipoproteins wurden keine Geschlechtsunterschiede bemerkt. Die Konzentrationen von Gesamt-Cholesterin, Triglyceriden, Apolipoprotein A-I und B im Seilim sowie das Verhältnis Gesamt-Cholesterin/Triglyceride in den VLDL ließen nicht zwischen ,*sinking prae-ß"-positiv oder -negativ unterscheiden. Bei allen Familienangehörigen wurde das Lp(a)-Antigen...

Serum Lp_(a) levels have been measured in a family kindred of three generations by Laurell electrophoresis. It was found that individuals with Lp_(a) levels exceeding 30 mg/dl exhibited an extra pre-beta-band in agarose gel electrophoresis (sinking pre-beta positive), and a significant positive correlation existed between serum Lp_(a) levels and age. A positive correlation between Lp_(a) and total serum cholesterol was observed only in sinking pre-beta-positive individuals, but not in sinking pre-β-negative individuals with Lp_(a) levels of less than 30 mg/dl. These findings are not contradictory to the assumption that Lp_(a) might be an independent rise factor for atherosclerosis.

Two electrophoretic populations of very low density lipoprotein are frequently observed in both normal and hyperlipidemic human sera. This gives the appearance of two pre-beta bands, called the "double pre-beta lipoprotein phenomenon." The slow and fast bands forming the double pre-beta lipoprotein were isolated by ultracentrifugation in the zonal rotor under rate flotation conditions. On the basis of the effluent position, the slow band showed a lower flotation coefficient than the fast one. The lipid and apoprotein composition of the two very low density lipoprotein populations isolated by zonal ultracentrifugation was in close agreement with those obtained by preparative agarose gel electrophoresis. The slow and fast pre-beta fractions had the same triglyceride fatty acid composition. Both fractions contained only higher molecular weight apo B-100, while the slow fraction was relatively enriched in apo E and apo C-lll. Since the slow pre-beta fraction showed the typical properties of the remnant particle, studying this fraction could clarify the possible relationship between remnant lipoproteins and atherogenesis. Zonal rotor ultracentrifugation may be useful to characterize remnant particles in normal and hyperlipidemic subjects. (Arteriosclerosis 4:598-603, November/December 1984) T wo separate populations of very low density lipoprotein (VLDL) that showed fast and slow prebeta mobility upon agarose gel electrophoresis were isolated by preparative agarose gel electrophoresis and characterized in our laboratory in 1977. 1The lipid and protein composition of the slow moving pre-beta component is similar to that of remnant particles because the slow moving component is poor (contains a low amount) in triglycerides and apo C and it is rich (contains a high amount) in cholesteryl esters and arginine-rich proteins.However, it should be stressed that these two VLDL particles are clearly distinguishable from the beta VLDL of dysbetalipoproteinemia (Type III) be- cause of two main characteristics: 1) the electrophoretic mobility of the VLDL particles is strictly pre-beta rather than beta, and 2) the isoelectric focusing (IEF) pattern of the apoprotein E in the VLDL particles is normal. The separation and characterization of remnant particles similar to those presented by double prebeta lipoproteinemia (DPBL), sometimes called late pre-beta lipoproteinemia, 2 is important because of the possible relationships between remnant particle accumulation and the development of atherosclerosis. Clinical studies show a very high prevalence of DPBL in uremia and hypothyroidism, conditions that are frequently associated with atherosclerotic complications.*- 5The present study was undertaken to find a faster and simpler method than the one we had previously used (preparative agarose gel electrophoresis 1 ) to isolate these two electrophoretic VLDL populations. We found that zonal rotor ultracentrifugation under flotation conditions enabled us to indirectly calculate the flotation coefficients of the two VLDL components and to mea...