Transthyretin in high density lipoproteins: Association with apolipoprotein A-I

Mónica Mendes Sousa, Lars Berglund, Maria João Saraiva

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Previous studies have revealed the presence of transthyretin (TTR) on lipoproteins. To further address this issue, we fractionated plasma lipoproteins from 9 normal individuals, 10 familial amyloidotic polyneuropathy (FAP) patients, and 19 hyperlipidemic subjects using gel filtration. In the majority of the subjects, as well as in 9 of the 10 FAP patients and 14 of the 19 patients with hyperlipidemia, TTR was detected by ELISA in the high density lipoprotein (HDL) fraction. The presence of TTR in HDL was confirmed by direct sequencing and by immunoblotting; using non- reducing conditions, TTR was found by immunoblotting in a high molecular weight complex, which reacted also for apolipoprotein A-I (apoA-I). The amount of TTR present in HDL (HDL-TTR), as quantified by ELISA corresponded to 1-2% of total plasma TTR. However, no detectable TTR levels were found in HDL fraction from 6 of the hyperlipidemic subjects. No correlation was found between the lack of TTR in HDL and plasma levels of total, LDL-, or HDL- associated cholesterol as well as levels of apoA-I and total plasma TTR. Ligand binding experiments showed that radiolabeled TTR binds to the HDL fraction of individuals with HDL-TTR but not to the corresponding fractions of individuals devoid of HDL-TTR, suggesting that HDL composition may interfere with TTR binding. The component(s) to which TTR binds in the HDL fraction were investigated. Polyclonal antibody against apoA-I was able to block the interaction of TTR with HDL, suggesting that the interaction of TTR with the HDL particle occurs via apoA-I. This hypothesis was further demonstrated by showing the formation of a complex of TTR with HDL and apoA-I by crosslinking experiments. Furthermore, anti-apoA-I immunoblot under native conditions suggested the existence of differences in HDL particle properties and/or stability between individuals with and without HDL-TTR.

Original languageEnglish (US)
Pages (from-to)58-65
Number of pages8
JournalJournal of Lipid Research
Volume41
Issue number1
StatePublished - Jan 2000
Externally publishedYes

Keywords

  • Amyloidosis
  • Apolipoprotein A-I
  • High density lipoproteins
  • Transthyretin

ASJC Scopus subject areas

  • Endocrinology

Fingerprint Dive into the research topics of 'Transthyretin in high density lipoproteins: Association with apolipoprotein A-I'. Together they form a unique fingerprint.

  • Cite this