Transthyretin proteins regulate angiogenesis by conferring different molecular identities to endothelial cells

R.J. Nunes, P. De Oliveira, A. Lages, J.D. Becker, P. Marcelino, E. Barroso, R. Perdigoto, J.W. Kelly, A. Quintas, S.C.R. Santos

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Familial amyloidotic polyneuropathy (FAP) has a high prevalence in Portugal, and the most common form of hereditary amyloidosis is caused by an amyloidogenic variant of transthyretin (TTR) with a substitution of methionine for valine at position30 (V30M). Until now, the available efficient therapy isliver transplantation, when performed in an early phase of the onset of the disease symptoms. However, transplanted FAP patients have a significantly higher incidence of early hepatic artery thrombosis compared with non-FAP transplanted patients. Because FAP was described as an independent risk factor for early hepatic artery thrombosis, more studies to understand the underlying mechanisms involved in this outcome are of the utmost importance. Knowing that the liver is the major site for TTR production, we investigated the biological effects of TTR proteinsinthe vasculature and on angiogenesis. In this study, we identified genes differentially expressed in endothelial cells exposed to the WT or V30M tetramer. We found that endothelial cells may acquire different molecular identities when exposedto these proteins, and consequently TTR could regulate angiogenesis. Moreover, we show that V30M decreases endothelial survival by inducing apoptosis, and it inhibits migration. These findings provide new knowledge that may have critical implications in the prevention of early hepatic artery thrombosis in FAP patients after liver transplantation. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.
Original languageEnglish
Pages (from-to)31752-31760
Number of pages9
JournalJournal of Biological Chemistry
Issue number44
Publication statusPublished - 2013


  • Biological effects
  • Disease symptoms
  • Familial amyloidotic polyneuropathy
  • Hepatic artery
  • Liver transplantation
  • Molecular identities
  • Risk factors
  • Transthyretin
  • Amino acids
  • Blood vessels
  • Cell death
  • Disease control
  • Diseases
  • Endothelial cells
  • Proteins
  • Liver
  • prealbumin
  • antiangiogenic activity
  • apoptosis
  • article
  • biological activity
  • cell migration
  • cell survival
  • controlled study
  • down regulation
  • endothelium cell
  • gene expression regulation
  • human
  • human cell
  • nucleotide sequence
  • priority journal
  • protein synthesis
  • Angiogenesis
  • Endothelial Cell
  • Familial Amyloidotic Polyneuropathy
  • Gene Expression
  • Microarray
  • Vascular Biology
  • Allografts
  • Amino Acid Substitution
  • Amyloid Neuropathies, Familial
  • Apoptosis
  • Cell Survival
  • Cells, Cultured
  • Gene Expression Regulation
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Liver Transplantation
  • Mutation, Missense
  • Neovascularization, Physiologic
  • Prealbumin
  • Thrombosis


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