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Cholesterol Dependence of Vascular ERK1/2 Activation and Growth in Response to Stretch. Role of Endothelin-1.

Zeidan, Asad LU ; Broman, Jonas LU ; Hellstrand, Per LU and Swärd, Karl LU (2003) In Arteriosclerosis, Thrombosis and Vascular Biology 23(9). p.1528-1534
Abstract
Objective— Stretch-induced growth of the vascular wall plays a role in hypertension and neointima formation. Its signal pathways involve integrins, cytoskeleton, membrane receptors, and ion channels, some of which are organized in cholesterol-rich, membrane domains such as lipid rafts or caveolae. This study tested the role of rafts/caveolae in stretch-induced vascular growth by manipulation of membrane cholesterol contents.



Methods and Results— Growth and protein synthesis were induced by mechanical stretch of rat portal veins in vitro. Sucrose gradient centrifugation showed stretch-induced tyrosine phosphorylation primarily in fractions containing caveolin-1. Disruption of membrane caveolae with use of... (More)
Objective— Stretch-induced growth of the vascular wall plays a role in hypertension and neointima formation. Its signal pathways involve integrins, cytoskeleton, membrane receptors, and ion channels, some of which are organized in cholesterol-rich, membrane domains such as lipid rafts or caveolae. This study tested the role of rafts/caveolae in stretch-induced vascular growth by manipulation of membrane cholesterol contents.



Methods and Results— Growth and protein synthesis were induced by mechanical stretch of rat portal veins in vitro. Sucrose gradient centrifugation showed stretch-induced tyrosine phosphorylation primarily in fractions containing caveolin-1. Disruption of membrane caveolae with use of methyl-ß-cyclodextrin (mßcd) reduced weight gain, protein synthesis, and DNA synthesis to levels in unstretched, control veins. These effects were partially reversed by restoration of cellular cholesterol contents. Inhibited growth was associated with abolished activation of extracellular signal–regulated kinase (ERK) 1/2 in response to stretch and endothelin-1 (ET-1) but not to angiotensin II. Inhibition of ET-1 type A (ETA) receptors by RF139317 or endothelin-converting enzyme by phosphoramidone abolished stretch-induced ERK1/2 activation, which was, however, unaffected by removal of the endothelium.



Conclusions— Stretch-induced growth signaling in vascular smooth muscle depends on cholesterol-rich, membrane microdomains by a mechanism involving ETA receptors that respond to endogenous ET-1 production. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
caveolae, cyclodextrin, portal vein, hypertrophy, ERK1/2
in
Arteriosclerosis, Thrombosis and Vascular Biology
volume
23
issue
9
pages
1528 - 1534
publisher
American Heart Association
external identifiers
  • wos:000185318700009
  • pmid:12907462
  • scopus:0043030323
ISSN
1524-4636
DOI
language
English
LU publication?
yes
id
958963e7-f29c-4526-89cd-6c3f1c584283 (old id 117452)
date added to LUP
2007-06-26 13:38:38
date last changed
2018-05-29 12:27:50
@article{958963e7-f29c-4526-89cd-6c3f1c584283,
  abstract     = {Objective— Stretch-induced growth of the vascular wall plays a role in hypertension and neointima formation. Its signal pathways involve integrins, cytoskeleton, membrane receptors, and ion channels, some of which are organized in cholesterol-rich, membrane domains such as lipid rafts or caveolae. This study tested the role of rafts/caveolae in stretch-induced vascular growth by manipulation of membrane cholesterol contents.<br/><br>
<br/><br>
Methods and Results— Growth and protein synthesis were induced by mechanical stretch of rat portal veins in vitro. Sucrose gradient centrifugation showed stretch-induced tyrosine phosphorylation primarily in fractions containing caveolin-1. Disruption of membrane caveolae with use of methyl-ß-cyclodextrin (mßcd) reduced weight gain, protein synthesis, and DNA synthesis to levels in unstretched, control veins. These effects were partially reversed by restoration of cellular cholesterol contents. Inhibited growth was associated with abolished activation of extracellular signal–regulated kinase (ERK) 1/2 in response to stretch and endothelin-1 (ET-1) but not to angiotensin II. Inhibition of ET-1 type A (ETA) receptors by RF139317 or endothelin-converting enzyme by phosphoramidone abolished stretch-induced ERK1/2 activation, which was, however, unaffected by removal of the endothelium.<br/><br>
<br/><br>
Conclusions— Stretch-induced growth signaling in vascular smooth muscle depends on cholesterol-rich, membrane microdomains by a mechanism involving ETA receptors that respond to endogenous ET-1 production.},
  author       = {Zeidan, Asad and Broman, Jonas and Hellstrand, Per and Swärd, Karl},
  issn         = {1524-4636},
  keyword      = {caveolae,cyclodextrin,portal vein,hypertrophy,ERK1/2},
  language     = {eng},
  number       = {9},
  pages        = {1528--1534},
  publisher    = {American Heart Association},
  series       = {Arteriosclerosis, Thrombosis and Vascular Biology},
  title        = {Cholesterol Dependence of Vascular ERK1/2 Activation and Growth in Response to Stretch. Role of Endothelin-1.},
  url          = {http://dx.doi.org/},
  volume       = {23},
  year         = {2003},
}