Caveolin-1 can regulate vascular smooth muscle cell fate by switching platelet-derived growth factor signaling from a proliferative to an apoptotic pathway

Timothy E. Peterson, Maria E. Guicciardi, Rajiv Gulati, Laurel S. Kleppe, Cheryl S. Mueske, Martina Mookadam, Grzegorz Sowa, Gregory James Gores, William C. Sessa, Robert D. Simari

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Background - Caveolin-1 is a regulator of signaling events originating from plasma membrane microdomains termed caveolae. This study was performed to determine the regulatory role of caveolin-1 on the proliferative events induced by platelet-derived growth factor (PDGF) in vascular smooth muscle cells (VSMCs). Methods and Results - Treatment of VSMCs with PDGF for 24 hours resulted in a loss of caveolin-1 protein expression and plasma membrane-associated caveolae, despite a 3-fold increase in caveolin-1 mRNA. Pretreatment of VSMCs with chloroquine, an inhibitor of lysosomal function, inhibited the PDGF-induced loss of caveolin-1. These studies demonstrated that caveolin-1 was a target of PDGF signaling events. Adenoviral overexpression of caveolin-1 was associated with a switch in PDGF-induced signaling events from a proliferative response to an apoptotic response. This overexpression inhibited PDGF-induced expression of cyclin D1 in the presence of unaffected mitogen-activated protein kinase activation. Conclusions - Taken together, these studies suggest that caveolin-1 is an inhibitor of PDGF proliferative responses and might be capable of transforming PDGF-induced proliferative signals into death signals.

Original languageEnglish (US)
Pages (from-to)1521-1527
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume23
Issue number9
DOIs
StatePublished - Sep 1 2003

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Caveolin 1
Platelet-Derived Growth Factor
Vascular Smooth Muscle
Smooth Muscle Myocytes
Caveolae
Cell Membrane
Membrane Microdomains
Caveolins
Cyclin D1
Chloroquine
Transforming Growth Factors
Mitogen-Activated Protein Kinases
Messenger RNA

Keywords

  • Apoptosis
  • Caveolae
  • Platelet-derived growth factor
  • Proliferation
  • Smooth muscle

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Caveolin-1 can regulate vascular smooth muscle cell fate by switching platelet-derived growth factor signaling from a proliferative to an apoptotic pathway. / Peterson, Timothy E.; Guicciardi, Maria E.; Gulati, Rajiv; Kleppe, Laurel S.; Mueske, Cheryl S.; Mookadam, Martina; Sowa, Grzegorz; Gores, Gregory James; Sessa, William C.; Simari, Robert D.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 23, No. 9, 01.09.2003, p. 1521-1527.

Research output: Contribution to journalArticle

Peterson, Timothy E. ; Guicciardi, Maria E. ; Gulati, Rajiv ; Kleppe, Laurel S. ; Mueske, Cheryl S. ; Mookadam, Martina ; Sowa, Grzegorz ; Gores, Gregory James ; Sessa, William C. ; Simari, Robert D. / Caveolin-1 can regulate vascular smooth muscle cell fate by switching platelet-derived growth factor signaling from a proliferative to an apoptotic pathway. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2003 ; Vol. 23, No. 9. pp. 1521-1527.
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