| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Departments of 1Molecular Pharmacology and Medicine and 2Urology, Albert Einstein College of Medicine, Bronx, New York; 3Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania; and 4Muscular and Neurodegenerative Disease Unit, University of Genoa, and G. Gaslini Pediatric Institute, Genoa, Italy
Submitted 2 November 2005 ; accepted in final form 10 January 2006
We previously showed that ablation of caveolin-1 (Cav-1) gene expression in mice promotes neointimal hyperplasia in vivo, a phenomenon normally characterized by smooth muscle cell (SMC) migration and proliferation. Whether these defects are cell autonomous, i.e., due to loss of Cav-1 within SMCs or loss of Cav-1 expression in other adjacent cell types in vivo, remains unknown. Cav-1 has been shown to associate with receptors for many vasoactive factors on the SMC surface. Therefore, Cav-1 might be an important regulator of SMC proliferation, migration, and signal transduction. To mechanistically dissect the role of Cav-1 in SMC signaling, we isolated SMCs from the aortas (AoSMCs) of Cav-1-deficient (Cav-1–/–) mice and characterized these cells with respect to their proliferation, migration, and Ca2+ response to an important vasoactive factor, endothelin-1 (ET-1). 5-Bromo-2'-deoxyuridine incorporation and a wound-healing assay showed an increase in proliferation and migration rates in Cav-1–/– compared with wild-type (Cav-1+/+) AoSMCs. Cav-1–/– AoSMCs demonstrated upregulation of phosphorylated ERK1/2, cyclin D1, and proliferating cell nuclear antigen and reduced expression of the cyclin-dependent kinase inhibitor p27Kip1. The Ca2+ response was examined in the presence of ET-1 and assessed by confocal microscopy with the Ca2+-sensitive fluorescent probe fluo 3. When treated with ET-1, Cav-1–/– AoSMCs exhibited a faster and larger increase in free intracellular Ca2+ than Cav-1+/+ cells. The ET-1-induced response in Cav-1–/– cells was mediated by the ETB receptor, as shown using the ETB receptor antagonist BQ-788 and the ETA receptor antagonist BQ-123. In Cav-1–/– cells, ETA receptor expression was reduced and ETB receptor expression was upregulated. Therefore, Cav-1 ablation increased the ET-1-induced Ca2+ response in SMCs by altering the type and expression level of the ET receptor (i.e., receptor isoform switching). These data suggest a novel regulatory role for Cav-1 in SMCs with respect to their proliferation, migration, and Ca2+-mediated signaling.
vascular disease; calcium response; endothelin receptors; neointimal hyperplasia; caveolae; caveolin
This article has been cited by other articles:
|
|
 |
|
  T. R. Lizarbe, C. Garcia-Rama, C. Tarin, M. Saura, E. Calvo, J. A. Lopez, C. Lopez-Otin, A. R. Folgueras, S. Lamas, and C. Zaragoza Nitric oxide elicits functional MMP-13 protein-tyrosine nitration during wound repair FASEB J, September 1, 2008; 22(9): 3207 - 3215. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Huang, P. M. Kaminski, J. G. Edwards, A. Yeh, M. S. Wolin, W. H. Frishman, M. H. Gewitz, and R. Mathew Pyrrolidine dithiocarbamate restores endothelial cell membrane integrity and attenuates monocrotaline-induced pulmonary artery hypertension Am J Physiol Lung Cell Mol Physiol, June 1, 2008; 294(6): L1250 - L1259. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Albinsson, I. Nordstrom, K. Sward, and P. Hellstrand Differential dependence of stretch and shear stress signaling on caveolin-1 in the vascular wall Am J Physiol Cell Physiol, January 1, 2008; 294(1): C271 - C279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Predescu, D. N. Predescu, and A. B. Malik Molecular determinants of endothelial transcytosis and their role in endothelial permeability Am J Physiol Lung Cell Mol Physiol, October 1, 2007; 293(4): L823 - L842. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Albinsson, Y. Shakirova, A. Rippe, M. Baumgarten, B.-I. Rosengren, C. Rippe, R. Hallmann, P. Hellstrand, B. Rippe, and K. Sward Arterial remodeling and plasma volume expansion in caveolin-1-deficient mice Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1222 - R1231. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kamishima, T. Burdyga, J. A. Gallagher, and J. M. Quayle Caveolin-1 and caveolin-3 regulate Ca2+ homeostasis of single smooth muscle cells from rat cerebral resistance arteries Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H204 - H214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Grande-Garcia, A. Echarri, J. de Rooij, N. B. Alderson, C. M. Waterman-Storer, J. M. Valdivielso, and M. A. del Pozo Caveolin-1 regulates cell polarization and directional migration through Src kinase and Rho GTPases J. Cell Biol., May 21, 2007; 177(4): 683 - 694. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Tosun, Y. Erac, C. Selli, and N. Karakaya Sarcoplasmic-endoplasmic reticulum Ca2+-ATPase inhibition prevents endothelin A receptor antagonism in rat aorta Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1961 - H1966. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-F. Jasmin, I. Mercier, J. Dupuis, H. B. Tanowitz, and M. P. Lisanti Short-Term Administration of a Cell-Permeable Caveolin-1 Peptide Prevents the Development of Monocrotaline-Induced Pulmonary Hypertension and Right Ventricular Hypertrophy Circulation, August 29, 2006; 114(9): 912 - 920. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
