Document Detail


Inhibition of intimal hyperplasia after stenting by over-expression of p15: A member of the INK4 family of cyclin-dependent kinase inhibitors.
MedLine Citation:
PMID:  21081134     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
We evaluated the role of p15(Ink4), a member of the INK4 family of CDK inhibitors on vascular smooth muscle cells (VSMCs) proliferation, cell cycle progression and intimal hyperplasia after stenting. Aortic VSMCs transduced with either adenovirus encoding for p15(Ink4) or β-galactosidase were assessed for DNA synthesis, cell cycle progression, and pRb phosphorylation. Rabbit carotid arteries were stented and treated with peri-adventitial delivery of saline or adenovirus encoding for p15(Ink4) or β-galactosidase. p15(Ink4) transgene and protein expression were evaluated at 24 h and 72 h, respectively. In-stent cell proliferation was evaluated by BrdU at day 7. Histomorphometric analysis of in-stent intimal hyperplasia was performed at 10weeks. Human p15(Ink4) DNA was detected in transduced VSMCs at 24h. p15(Ink4) over-expression reduced VSMCs DNA synthesis by 60%. Cell cycle progression was inhibited, with a 30% increase in G1 population accompanied by inhibition of pRb phosphorylation. Human p15(Ink4) transgene was identified in transduced stented arteries but not in control arteries. p15(Ink4) immunostaining was increased and cell proliferation significantly reduced by 50% in p15(Ink4) transduced arteries. Intimal cross-sectional area (CSA) of p15(Ink4)-treated group was significantly lower than the β-gal treated and non-transduced groups (p=0.008). There were no differences in the intimal or medial inflammatory response between groups. p15(Ink4) over-expression blocks cell cycle progression leading to inhibition of VSMCs proliferation. Peri-adventitial delivery of p15(Ink4) significantly inhibits in-stent intimal hyperplasia.
Authors:
Amit Segev; Nafiseh Nili; Beiping Qiang; Azriel B Osherov; Frank J Giordano; Ronen Jaffe; Jack Gauldie; John D Sparkes; Ashley R Fraser; Michelle Ladouceur-Wodzak; Jagdish Butany; Bradley H Strauss
Related Documents :
21294974 - Transdifferentiation of clara cell 10-kda protein secreting cells in experimental aller...
19287994 - Alpha-smooth muscle actin-positive fibroblasts promote biliary cell proliferation and c...
11172964 - Rhenium-188 for inhibition of human aortic smooth muscle cell proliferation.
3089294 - Effect of elastase on prostacyclin synthesis in aortic smooth muscle cells.
10968634 - Changes in the physiological and agricultural characteristics of peat-based bradyrhizob...
17027224 - Characterization of multipotent cells from human adult hair follicles.
Publication Detail:
Type:  Journal Article     Date:  2010-11-21
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  50     ISSN:  1095-8584     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-02-08     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  417-25     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Interventional Cardiology Unit, Chaim Sheba Medical Center, Tel Hashomer, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel; The Roy and Ann Foss Interventional Cardiology Research Program, Terrence Donnelly Heart Center, St. Michael's Hospital, Toronto, Canada.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Fish trophic level and the similarity of non-specific larval parasite assemblages.
Next Document:  Natural and synthetic corticosteroids inhibit uptake(2)-mediated transport in CNS neurons.