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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/5075932
- author
- 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
- organization
- publishing date
- 2014
- 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
- Portland Press
- external identifiers
-
- wos:000347799400007
- scopus:84915821316
- pmid:25301005
- 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
- 2016-04-01 13:39:16
- date last changed
- 2022-01-27 20:20:39
@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}},
keywords = {{caveolin-1; cell cycle; ornithine decarboxylase; polyamine transporter; polyamine; vascular smooth muscle cell}},
language = {{eng}},
pages = {{729--741}},
publisher = {{Portland Press}},
series = {{Bioscience Reports}},
title = {{Vascular smooth muscle cell proliferation depends on caveolin-1-regulated polyamine uptake}},
url = {{https://lup.lub.lu.se/search/files/3501715/7761448}},
doi = {{10.1042/BSR20140140}},
volume = {{34}},
year = {{2014}},
}