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Vascular smooth muscle cell proliferation depends on caveolin-1-regulated polyamine uptake

Grossi, Mario LU ; Rippe, Catarina LU ; Sathanoori, Ramasri LU ; Swärd, Karl LU ; Forte, Amalia; Erlinge, David LU ; Persson, Lo LU ; Hellstrand, Per LU and Nilsson, Bengt-Olof LU (2014) In Bioscience Reports 34. p.729-741
Abstract
Much evidence highlights the importance of polyamines for VSMC (vascular smooth muscle cell) proliferation and migration. Cav-1 (caveolin-1) was recently reported to regulate polyamine uptake in intestinal epithelial cells. The aim of the present study was to assess the importance of Cav-1 for VSMC polyamine uptake and its impact on cell proliferation and migration. Cav-1 KO (knockout) mouse aortic cells showed increased polyamine uptake and elevated proliferation and migration compared with WT (wild-type) cells. Both Cav-1 KO and WT cells expressed the smooth muscle differentiation markers SM22 and calponin. Cell-cycle phase distribution analysis revealed a higher proportion of Cav-1 KO than WT cells in the S phase. Cav-1 KO cells were... (More)
Much evidence highlights the importance of polyamines for VSMC (vascular smooth muscle cell) proliferation and migration. Cav-1 (caveolin-1) was recently reported to regulate polyamine uptake in intestinal epithelial cells. The aim of the present study was to assess the importance of Cav-1 for VSMC polyamine uptake and its impact on cell proliferation and migration. Cav-1 KO (knockout) mouse aortic cells showed increased polyamine uptake and elevated proliferation and migration compared with WT (wild-type) cells. Both Cav-1 KO and WT cells expressed the smooth muscle differentiation markers SM22 and calponin. Cell-cycle phase distribution analysis revealed a higher proportion of Cav-1 KO than WT cells in the S phase. Cav-1 KO cells were hyper-proliferative in the presence but not in the absence of extracellular polyamines, and, moreover, supplementation with exogenous polyamines promoted proliferation in Cav-1 KO but not in WT cells. Expression of the solute carrier transporters Slc7a1 and Slc43a1 was higher in Cav-1 KO than in WT cells. ODC (ornithine decarboxylase) protein and mRNA expression as well as ODC activity were similar in Cav-1 KO and WT cells showing unaltered synthesis of polyamines in Cav-1 KO cells. Cav-1 was reduced in migrating cells in vitro and in carotid lesions in vivo. Our data show that Cav-1 negatively regulates VSMC polyamine uptake and that the proliferative advantage of Cav-1 KO cells is critically dependent on polyamine uptake. We provide proof-of-principle for targeting Cav-1-regulated polyamine uptake as a strategy to fight unwanted VSMC proliferation as observed in restenosis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
caveolin-1, cell cycle, ornithine decarboxylase, polyamine transporter, polyamine, vascular smooth muscle cell
in
Bioscience Reports
volume
34
pages
729 - 741
publisher
Kluwer
external identifiers
  • wos:000347799400007
  • scopus:84915821316
ISSN
0144-8463
DOI
10.1042/BSR20140140
language
English
LU publication?
yes
id
ea596315-fe3a-4ea7-ac08-29bcbf918680 (old id 5075932)
date added to LUP
2015-03-02 07:03:43
date last changed
2017-11-05 04:00:26
@article{ea596315-fe3a-4ea7-ac08-29bcbf918680,
  abstract     = {Much evidence highlights the importance of polyamines for VSMC (vascular smooth muscle cell) proliferation and migration. Cav-1 (caveolin-1) was recently reported to regulate polyamine uptake in intestinal epithelial cells. The aim of the present study was to assess the importance of Cav-1 for VSMC polyamine uptake and its impact on cell proliferation and migration. Cav-1 KO (knockout) mouse aortic cells showed increased polyamine uptake and elevated proliferation and migration compared with WT (wild-type) cells. Both Cav-1 KO and WT cells expressed the smooth muscle differentiation markers SM22 and calponin. Cell-cycle phase distribution analysis revealed a higher proportion of Cav-1 KO than WT cells in the S phase. Cav-1 KO cells were hyper-proliferative in the presence but not in the absence of extracellular polyamines, and, moreover, supplementation with exogenous polyamines promoted proliferation in Cav-1 KO but not in WT cells. Expression of the solute carrier transporters Slc7a1 and Slc43a1 was higher in Cav-1 KO than in WT cells. ODC (ornithine decarboxylase) protein and mRNA expression as well as ODC activity were similar in Cav-1 KO and WT cells showing unaltered synthesis of polyamines in Cav-1 KO cells. Cav-1 was reduced in migrating cells in vitro and in carotid lesions in vivo. Our data show that Cav-1 negatively regulates VSMC polyamine uptake and that the proliferative advantage of Cav-1 KO cells is critically dependent on polyamine uptake. We provide proof-of-principle for targeting Cav-1-regulated polyamine uptake as a strategy to fight unwanted VSMC proliferation as observed in restenosis.},
  author       = {Grossi, Mario and Rippe, Catarina and Sathanoori, Ramasri and Swärd, Karl and Forte, Amalia and Erlinge, David and Persson, Lo and Hellstrand, Per and Nilsson, Bengt-Olof},
  issn         = {0144-8463},
  keyword      = {caveolin-1,cell cycle,ornithine decarboxylase,polyamine transporter,polyamine,vascular smooth muscle cell},
  language     = {eng},
  pages        = {729--741},
  publisher    = {Kluwer},
  series       = {Bioscience Reports},
  title        = {Vascular smooth muscle cell proliferation depends on caveolin-1-regulated polyamine uptake},
  url          = {http://dx.doi.org/10.1042/BSR20140140},
  volume       = {34},
  year         = {2014},
}