Apolipoprotein(a) kringle 4-containing fragments in human urine: Relationship to plasma levels of lipoprotein(a)

Vincent Mooser, Miguel C. Seabra, Moeen Abedin, Katherine T. Landschulz, Santica Marcovina, Helen H. Hobbs

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Apo(a) is a large glycoprotein of unknown function that circulates in plasma as part of lipoprotein(a). Apo(a) is structurally related to plasminogen and contains at least 10 kringle (K)4 repeats (type 1-10), a K5 repeat and sequences similar to the protease domain of plasminogen. Plasminogen generates two biologically active peptides: plasmin and angiostatin, a kringle-containing peptide. As a first step in determining if apo(a) generates a similar kringle-containing peptide, human urine was immunologically examined. Fragments ranging in size from 85 to 215 kD were immunodetected using antibodies directed against epitopes in the K4-type 2 repeat, but not the K4-type 9 repeat or protease domain. NH2-terminal sequence analysis revealed sequences specific for the K4-type 1 repeat, confirming that the fragments are from the NH2 terminus of the K4 array. The amount of urinary apo(a) rose in proportion to the plasma lipoprotein(a) concentration. Even individuals with trace to no apo(a) in plasma had immunodetectable apo(a) fragments in their urine. Intravenous administration of the human urinary apo(a) into mice resulted in the rapid appearance of the same sized fragments in the urine. These findings suggest that the apo(a) fragments found in urine are formed extrarenally and then excreted by the kidney.

Original languageEnglish (US)
Pages (from-to)858-864
Number of pages7
JournalJournal of Clinical Investigation
Volume97
Issue number3
StatePublished - Feb 1 1996

Fingerprint

Kringles
Apoprotein(a)
Lipoprotein(a)
Plasminogen
Urine
Peptides
Peptide Hydrolases
Angiostatins
Fibrinolysin
Intravenous Administration
Sequence Analysis
Epitopes
Glycoproteins
Kidney
Antibodies

Keywords

  • angiostatin
  • apolipoprotein(a)
  • kringles
  • lipoprotein(a)
  • plasminogen

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Apolipoprotein(a) kringle 4-containing fragments in human urine : Relationship to plasma levels of lipoprotein(a). / Mooser, Vincent; Seabra, Miguel C.; Abedin, Moeen; Landschulz, Katherine T.; Marcovina, Santica; Hobbs, Helen H.

In: Journal of Clinical Investigation, Vol. 97, No. 3, 01.02.1996, p. 858-864.

Research output: Contribution to journalArticle

Mooser, Vincent ; Seabra, Miguel C. ; Abedin, Moeen ; Landschulz, Katherine T. ; Marcovina, Santica ; Hobbs, Helen H. / Apolipoprotein(a) kringle 4-containing fragments in human urine : Relationship to plasma levels of lipoprotein(a). In: Journal of Clinical Investigation. 1996 ; Vol. 97, No. 3. pp. 858-864.
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