Suppression of growth factor expression and human vascular smooth muscle cell growth by small interfering RNA targeting EGR-1

2007 ◽  
Vol 100 (6) ◽  
pp. 1526-1535 ◽  
Author(s):  
Roger G. Fahmy ◽  
Levon M. Khachigian
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Cell Growth ◽  
Smooth Muscle Cell ◽  
Small Interfering Rna ◽  
Rna Targeting ◽  
Smooth Muscle Cell Growth ◽  
Factor Expression ◽  
Growth Factor Expression ◽  
Interfering Rna

scholarly journals Ether-linked diglycerides inhibit vascular smooth muscle cell growth via decreased MAPK and PI3K/Akt signaling

2008 ◽  
Vol 295 (4) ◽  
pp. H1657-H1668 ◽  
Author(s):  
Kristy L. Houck ◽  
Todd E. Fox ◽  
Lakshman Sandirasegarane ◽  
Mark Kester
Keyword(s):  
Smooth Muscle ◽  
Growth Factors ◽  
Growth Factor ◽  
Cell Growth ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cell ◽  
Inflammatory Cytokines ◽  
Muscle Cell ◽  
Akt Signaling ◽  
Smooth Muscle Cell Growth

Diglycerides (DGs) are phospholipid-derived second messengers that regulate PKC-dependent signaling pathways. Distinct species of DGs are generated from inflammatory cytokines and growth factors. Growth factors increase diacyl- but not ether-linked DG species, whereas inflammatory cytokines predominately generate alkyl, acyl- and alkenyl, acyl-linked DG species in rat mesenchymal cells. These DG species have been shown to differentially regulate protein kinase C (PKC) isotypes. Ester-linked diacylglycerols activate PKC-ε and cellular proliferation in contrast to ether-linked DGs, which lead to growth arrest through the inactivation of PKC-ε. It is now hypothesized that ether-linked DGs inhibit mitogenesis through the inactivation of ERK and/or Akt signaling cascades. We demonstrate that cell-permeable ether-linked DGs reduce vascular smooth muscle cell growth by inhibiting platelet-derived growth factor-stimulated ERK in a PKC-ε-dependent manner. This inhibition is specific to the ERK pathway, since ether-linked DGs do not affect growth factor-induced activation of other family members of the MAPKs, including p38 MAPK and c-Jun NH2-terminal kinases. We also demonstrate that ether-linked DGs reduce prosurvival phosphatidylinositol 3-kinase (PI3K)/Akt signaling, independent of PKC-ε, by diminishing an interaction between the subunits of PI3K and not by affecting protein phosphatase 2A or lipid (phosphatase and tensin homologue deleted in chromosome 10) phosphatases. Taken together, our studies identify ether-linked DGs as potential adjuvant therapies to limit vascular smooth muscle migration and mitogenesis in atherosclerotic and restenotic models.

scholarly journals Hepatoma-derived growth factor stimulates smooth muscle cell growth and is expressed in vascular development

2000 ◽  
Vol 105 (5) ◽  
pp. 567-575 ◽  
Author(s):  
Allen D. Everett ◽  
David R. Lobe ◽  
Martin E. Matsumura ◽  
Hideji Nakamura ◽  
Coleen A. McNamara
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Cell Growth ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Development ◽  
Smooth Muscle Cell Growth
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