Kringle-containing fragments of apolipoprotein(a) circulate in human plasma and are excreted into the urine

Vincent Mooser, Santica M. Marcovina, Ann L. White, Helen H. Hobbs

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Apolipoprotein(a) [apo(a)] contains multiple kringle 4 repeats and circulates as part of lipoprotein(a) [Lp(a)]. Apo(a) is synthesized by the liver but its clearance mechanism is unknown. Previously, we showed that kringle 4-containing fragments of apo(a) are present in human urine. To probe their origin, human plasma was examined and a series of apo(a) immunoreactive peptides larger in size than urinary fragments was identified. The concentration of apo(a) fragments in plasma was directly related to the plasma level of Lp(a) and the 24-h urinary excretion of apo(a). Individuals with low (< 2 mg/dl) plasma levels of Lp(a) had proportionally more apo(a) circulating as fragments in their plasma. Similar apo(a) fragments were identified in baboon plasma but not in conditioned media from primary cultures of baboon hepatocytes, suggesting that the apo(a) fragments are generated from circulating apo(a) or Lp(a). When apo(a) fragments purified from human plasma were injected intravenously into mice, a species that does not produce apo(a). apo(a) fragments similar to those found in human urine were readily detected in mouse urine. Thus, we propose that apo(a) fragments in human plasma are derived from circulating apo(a)/Lp(a) and are the source of urinary apo(a).

Original languageEnglish (US)
Pages (from-to)2414-2424
Number of pages11
JournalJournal of Clinical Investigation
Volume98
Issue number10
StatePublished - Nov 15 1996

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Kringles
Apoprotein(a)
Urine
Lipoprotein(a)
Papio

Keywords

  • heparin
  • kidney
  • lipoprotein(a)
  • monkey
  • mouse

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kringle-containing fragments of apolipoprotein(a) circulate in human plasma and are excreted into the urine. / Mooser, Vincent; Marcovina, Santica M.; White, Ann L.; Hobbs, Helen H.

In: Journal of Clinical Investigation, Vol. 98, No. 10, 15.11.1996, p. 2414-2424.

Research output: Contribution to journalArticle

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AB - Apolipoprotein(a) [apo(a)] contains multiple kringle 4 repeats and circulates as part of lipoprotein(a) [Lp(a)]. Apo(a) is synthesized by the liver but its clearance mechanism is unknown. Previously, we showed that kringle 4-containing fragments of apo(a) are present in human urine. To probe their origin, human plasma was examined and a series of apo(a) immunoreactive peptides larger in size than urinary fragments was identified. The concentration of apo(a) fragments in plasma was directly related to the plasma level of Lp(a) and the 24-h urinary excretion of apo(a). Individuals with low (< 2 mg/dl) plasma levels of Lp(a) had proportionally more apo(a) circulating as fragments in their plasma. Similar apo(a) fragments were identified in baboon plasma but not in conditioned media from primary cultures of baboon hepatocytes, suggesting that the apo(a) fragments are generated from circulating apo(a) or Lp(a). When apo(a) fragments purified from human plasma were injected intravenously into mice, a species that does not produce apo(a). apo(a) fragments similar to those found in human urine were readily detected in mouse urine. Thus, we propose that apo(a) fragments in human plasma are derived from circulating apo(a)/Lp(a) and are the source of urinary apo(a).

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