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Polyamine concentration is increased in thoracic ascending aorta of patients with bicuspid aortic valve

Forte, Amalia; Grossi, Mario LU ; Bancone, Ciro; Cipollaro, Marilena; de Feo, Marisa; Hellstrand, Per LU ; Persson, Lo LU ; Nilsson, Bengt Olof LU and della Corte, Alessandro (2017) In Heart and Vessels p.1-13
Abstract

Polyamines are cationic molecules synthesized via a highly regulated pathway, obtained from the diet or produced by the gut microbiota. They are involved in general molecular and cellular phenomena that play a role also in vascular disease. Bicuspid aortic valve (BAV) is a congenital malformation associated to a greater risk of thoracic ascending aorta (TAA) aneurysm, whose pathogenesis is not yet well understood. We focused on differential analysis of key members of polyamine pathway and on polyamine concentration in non-dilated TAA samples from patients with either stenotic tricuspid aortic valve (TAV) or BAV (diameter ≤ 45 mm), vs. normal aortas from organ donors, with the aim of revealing a potential involvement of polyamines in... (More)

Polyamines are cationic molecules synthesized via a highly regulated pathway, obtained from the diet or produced by the gut microbiota. They are involved in general molecular and cellular phenomena that play a role also in vascular disease. Bicuspid aortic valve (BAV) is a congenital malformation associated to a greater risk of thoracic ascending aorta (TAA) aneurysm, whose pathogenesis is not yet well understood. We focused on differential analysis of key members of polyamine pathway and on polyamine concentration in non-dilated TAA samples from patients with either stenotic tricuspid aortic valve (TAV) or BAV (diameter ≤ 45 mm), vs. normal aortas from organ donors, with the aim of revealing a potential involvement of polyamines in early aortopathy. Changes of gene expression in TAA samples were evaluated by RT-PCR. Changes of ornithine decarboxylase 1 (ODC1), a key enzyme in polyamine formation, and cationic amino acid transporter 1 (SLC7A1/CAT-1) expression were analyzed also by Western blot. ODC1 subcellular localization was assessed by immunohistochemistry. Polyamine concentration in TAA samples was evaluated by HPLC. BAV TAA samples showed an increased concentration of putrescine and spermidine vs. TAV and donor samples, together with a decreased mRNA level of polyamine anabolic enzymes and of the putative polyamine transporter SLC7A1/CAT-1. The catabolic enzyme spermidine/spermine N1-acetyltransferase 1 showed a significant mRNA increase in TAV samples only, together with a decreased concentration of spermine. The decreased expression of SLC7A1/CAT-1 and ODC1 mRNAs in BAV corresponded to increased or unchanged expression of the respective proteins. ODC was located mainly in smooth muscle cell (SMC) nucleus in TAV and donor samples, while it was present also in SMC cytoplasm in BAV samples, suggesting its activation. In conclusion, BAV, but not TAV non-dilated samples show increased polyamine concentration, accompanied by the activation of a regulatory negative feedback mechanism.

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author
organization
publishing date
type
Contribution to journal
publication status
in press
subject
keywords
Aneurysm, Aortopathy, Bicuspid aortic valve, Ornithine decarboxylase, Polyamines, Thoracic ascending aorta
in
Heart and Vessels
pages
13 pages
publisher
Springer
external identifiers
  • scopus:85034252593
ISSN
0910-8327
DOI
10.1007/s00380-017-1087-z
language
English
LU publication?
yes
id
e2d88a41-a3f9-4aad-84fb-c7bd121b70a5
date added to LUP
2017-12-14 14:41:53
date last changed
2018-01-07 12:28:49
@article{e2d88a41-a3f9-4aad-84fb-c7bd121b70a5,
  abstract     = {<p>Polyamines are cationic molecules synthesized via a highly regulated pathway, obtained from the diet or produced by the gut microbiota. They are involved in general molecular and cellular phenomena that play a role also in vascular disease. Bicuspid aortic valve (BAV) is a congenital malformation associated to a greater risk of thoracic ascending aorta (TAA) aneurysm, whose pathogenesis is not yet well understood. We focused on differential analysis of key members of polyamine pathway and on polyamine concentration in non-dilated TAA samples from patients with either stenotic tricuspid aortic valve (TAV) or BAV (diameter ≤ 45 mm), vs. normal aortas from organ donors, with the aim of revealing a potential involvement of polyamines in early aortopathy. Changes of gene expression in TAA samples were evaluated by RT-PCR. Changes of ornithine decarboxylase 1 (ODC1), a key enzyme in polyamine formation, and cationic amino acid transporter 1 (SLC7A1/CAT-1) expression were analyzed also by Western blot. ODC1 subcellular localization was assessed by immunohistochemistry. Polyamine concentration in TAA samples was evaluated by HPLC. BAV TAA samples showed an increased concentration of putrescine and spermidine vs. TAV and donor samples, together with a decreased mRNA level of polyamine anabolic enzymes and of the putative polyamine transporter SLC7A1/CAT-1. The catabolic enzyme spermidine/spermine N1-acetyltransferase 1 showed a significant mRNA increase in TAV samples only, together with a decreased concentration of spermine. The decreased expression of SLC7A1/CAT-1 and ODC1 mRNAs in BAV corresponded to increased or unchanged expression of the respective proteins. ODC was located mainly in smooth muscle cell (SMC) nucleus in TAV and donor samples, while it was present also in SMC cytoplasm in BAV samples, suggesting its activation. In conclusion, BAV, but not TAV non-dilated samples show increased polyamine concentration, accompanied by the activation of a regulatory negative feedback mechanism.</p>},
  author       = {Forte, Amalia and Grossi, Mario and Bancone, Ciro and Cipollaro, Marilena and de Feo, Marisa and Hellstrand, Per and Persson, Lo and Nilsson, Bengt Olof and della Corte, Alessandro},
  issn         = {0910-8327},
  keyword      = {Aneurysm,Aortopathy,Bicuspid aortic valve,Ornithine decarboxylase,Polyamines,Thoracic ascending aorta},
  language     = {eng},
  month        = {11},
  pages        = {1--13},
  publisher    = {Springer},
  series       = {Heart and Vessels},
  title        = {Polyamine concentration is increased in thoracic ascending aorta of patients with bicuspid aortic valve},
  url          = {http://dx.doi.org/10.1007/s00380-017-1087-z},
  year         = {2017},
}