Lipoprotein (a) is not a metabolic product of other lipoproteins containing apolipoprotein B

Krempler, Franz; Kostner, Gert M.; Bolzano, K; Sandhofer, F

doi:10.1016/0005-2760(79)90131-0

Cited by 100 publications

(31 citation statements)

References 24 publications

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“…In previous studies in our laboratory very low density lipoprotein (VLDL) from strongly Lp(a)-positive volunteers was radiolabelled, reinjected into the circulation and the fractional decay of radioactivity followed over time in VLDL, intermediate-density lipoprotein (IDL), LDL and Lp(a) [18]. These studies revealed that Lp(a) is not a direct metabolic product of VLDL, which led us to conclude that Lp(a) might be independently synthesized from triglyceride-rich lipoproteins and probably secreted directly from the liver.…”

Section: Metabolism Of Lp(a)mentioning

confidence: 99%

The assembly of lipoprotein Lp(a)

Frank¹,

Durovic²,

Kostner³

1996

Eur J Clin Investigation

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Section: Metabolism Of Lp(a)mentioning

confidence: 99%

The assembly of lipoprotein Lp(a)

Frank¹,

Durovic²,

Kostner³

1996

Eur J Clin Investigation

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“…Metabolic studies in humans have demonstrated that triglyceride-rich lipoproteins, which are well-established precursors of LDL, do not represent metabolic precursors for Lp(a) (Krempler et al, 1979;Sandholzer et al, 1992). The question of whether apo(a) forms a complex with apoB in hepatocytes or whether apo(a) binds to LDL only after its secretion to the interstitium or the plasma compartment remains open.…”

Section: University Of Innsbruckmentioning

confidence: 99%

High-Level Expression of Various Apolipoprotein (a) Isoforms by "Transferrinfection": The Role of Kringle IV Sequences in the Extracellular Association with Low-Density Lipoprotein

Frank

K²,

Durovic³

et al. 1994

Biochemistry

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Characterization of the assembly of lipoprotein(a) [Lp(a)] is of fundamental importance to understanding the biosynthesis and metabolism of this atherogenic lipoprotein. Since no established cell lines exist that express Lp(a) or apolipoprotein(a) [apo(a)], a "transferrinfection" system for apo(a) was developed utilizing adenovirus receptor-and transferrin receptor-mediated DNA uptake into cells. Using this method, different apo(a) cDNA constructions of variable length, due to the presence of 3, 5, 7,9, 15, or 18 internal kringle IV sequences, were expressed in cos-7 cells or C H O cells. All constructions contained kringle IV-36, which includes the only unpaired cysteine residue (Cys-4057) in apo(a). r-Apo(a) was synthesized as a precursor and secreted as mature apolipoprotein into the medium. When medium containing r-apo(a) with 9, 15, or 18 kringle IV repeats was mixed with normal human plasma LDL, stable complexes formed that had a bouyant density typical of Lp(a). Association was substantially decreased if Cys-4057 on r-apo(a) was replaced by Arg by site-directed mutagenesis or if Cys-4057 was chemically modified. Lack of association was also observed with r-apo(a) containing only 3, 5, or 7 kringle IV repeats without "unique kringle IV Sequences", although Cys-4057 was present in all of these constructions. Synthesis and secretion of r-apo(a) was not dependent on its sialic acid content. r-Apo(a) was expressed even more efficiently in sialylation-defective C H O cells than in wild-type C H O cells. In transfected C H O cells defective in the addition of N-acetylglucosamine, apo(a) secretion was found to be decreased by 50%. Extracellular association with LDL was not affected by the carbohydrate moiety of r-apo(a), indicating a protein-protein interaction between r-apo(a) and apoB. These results show that, besides kringle IV-36, other kringle IV sequences are necessary for the extracellular association of r-apo(a) with LDL. Changes in the carbohydrate moiety of apo(a), however, do not affect complex formation.Lipoprotein(a) [Lp(a)] is currently the subject of intensive investigation because elevated plasma concentrations of Lp-(a) represent an independent risk factor for myocardial infarction and stroke (Scanu & Fless, 1990;Utermann, 1989Utermann, , 1990Edelberg & Pizzo, 1991). Despite its clinical importance, the physiological function of Lp (a)

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“…It has been postulated that Lp(a) is not a metabolic product of other apo B-containing lipoproteins (chylomicrons, VLDL or LDL) and thus Lp(a) should be synthesized as a separate lipoprotein [5]. Furthermore Lp(a) is not converted into other lipoproteins [6].…”

Section: Isolation and Analysis Of Lipopro Teinsmentioning

confidence: 99%