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

Research output: Contribution to journalArticle

17 Citations (Scopus)
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Abstract

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
Volume288
Issue number44
DOIs
Publication statusPublished - 2013

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Prealbumin
Polyneuropathies
Endothelial Cells
Hepatic Artery
Thrombosis
Proteins
Familial Amyloidosis
Portugal
Valine
Methionine
Liver Transplantation
Transplantation
Apoptosis
Survival
Liver
Incidence
Genes

Keywords

  • 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

Cite this

Nunes, R.J. ; De Oliveira, P. ; Lages, A. ; Becker, J.D. ; Marcelino, P. ; Barroso, E. ; Perdigoto, R. ; Kelly, J.W. ; Quintas, A. ; Santos, S.C.R. / Transthyretin proteins regulate angiogenesis by conferring different molecular identities to endothelial cells. In: Journal of Biological Chemistry. 2013 ; Vol. 288, No. 44. pp. 31752-31760.
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Transthyretin proteins regulate angiogenesis by conferring different molecular identities to endothelial cells. / Nunes, R.J.; De Oliveira, P.; Lages, A.; Becker, J.D.; Marcelino, P.; Barroso, E.; Perdigoto, R.; Kelly, J.W.; Quintas, A.; Santos, S.C.R.

In: Journal of Biological Chemistry, Vol. 288, No. 44, 2013, p. 31752-31760.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Transthyretin proteins regulate angiogenesis by conferring different molecular identities to endothelial cells

AU - Nunes, R.J.

AU - De Oliveira, P.

AU - Lages, A.

AU - Becker, J.D.

AU - Marcelino, P.

AU - Barroso, E.

AU - Perdigoto, R.

AU - Kelly, J.W.

AU - Quintas, A.

AU - Santos, S.C.R.

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PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - Biological effects

KW - Disease symptoms

KW - Familial amyloidotic polyneuropathy

KW - Hepatic artery

KW - Liver transplantation

KW - Molecular identities

KW - Risk factors

KW - Transthyretin

KW - Amino acids

KW - Blood vessels

KW - Cell death

KW - Disease control

KW - Diseases

KW - Endothelial cells

KW - Proteins

KW - Liver

KW - prealbumin

KW - antiangiogenic activity

KW - apoptosis

KW - article

KW - biological activity

KW - cell migration

KW - cell survival

KW - controlled study

KW - down regulation

KW - endothelium cell

KW - gene expression regulation

KW - human

KW - human cell

KW - nucleotide sequence

KW - priority journal

KW - protein synthesis

KW - Angiogenesis

KW - Endothelial Cell

KW - Familial Amyloidotic Polyneuropathy

KW - Gene Expression

KW - Microarray

KW - Vascular Biology

KW - Allografts

KW - Amino Acid Substitution

KW - Amyloid Neuropathies, Familial

KW - Apoptosis

KW - Cell Survival

KW - Cells, Cultured

KW - Gene Expression Regulation

KW - Human Umbilical Vein Endothelial Cells

KW - Humans

KW - Liver Transplantation

KW - Mutation, Missense

KW - Neovascularization, Physiologic

KW - Prealbumin

KW - Thrombosis

U2 - 10.1074/jbc.M113.469858

DO - 10.1074/jbc.M113.469858

M3 - Article

VL - 288

SP - 31752

EP - 31760

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 44

ER -