Why are some amyloidoses systemic? Does hepatic "chaperoning at a distance" prevent cardiac deposition in a transgenic model of human senile systemic (transthyretin) amyloidosis?

ABSTRACT: In the human systemic amyloidoses caused by mutant or wild-type transthyretin (TTR), deposition occurs at a distance from the site of synthesis. The TTR synthesized and secreted by the hepatocyte circulates in plasma, then deposits in target tissues far from the producing cell, a pattern reproduced in mice transgenic for multiple copies of the human wild-type TTR gene. By 2 yr of age, half of the transgenic males show cardiac deposition resembling human senile systemic amyloidosis. However, as early as 3 mo of age, when there are no deposits, cardiac gene transcription differs from that of nontransgenic littermates, primarily in the expression of a large number of genes associated with inflammation and the immune response. At 24 mo, the hearts with histologically proven TTR deposits show e

SUBMITTER: Buxbaum JN 

PROVIDER: S-EPMC3360152 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature