Document Detail


Protein kinase C-delta mediates adventitial cell migration through regulation of monocyte chemoattractant protein-1 expression in a rat angioplasty model.
MedLine Citation:
PMID:  22328773     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: The adventitia is increasingly recognized as an important player during the development of intimal hyperplasia. However, the mechanism of adventitial cell recruitment to the subintimal space remains largely undefined. We have shown previously that gene transfer of protein kinase C-delta (PKCδ) increases apoptosis of smooth muscle cells following balloon injury. In the current study, we investigated a potential role of PKCδ in regulating the recruitment of adventitial cells.
METHODS AND RESULTS: Conditioned media from PKCδ-overexpressing smooth muscle cells stimulated migration and CCR2 expression of adventitial fibroblasts through a MCP-1 dependent mechanism. Following balloon injury of rat carotid arteries, overexpression of PKCδ in smooth muscle cells significantly increased MCP-1 and CCR2 expression and the number of adventitia-originated cells detected in the neointima. Administration of an anti-MCP-1 antibody markedly diminished the recruitment of adventitial cells. Combined PKCδ overexpression and anti-MCP-1 inhibited intimal hyperplasia more effectively than either approach alone.
CONCLUSIONS: Our data suggest that PKCδ regulates recruitment of adventitial cells to the neointima via a mechanism involving upregulation of the MCP-1/CCR2 signaling axis in injured arteries. Blockage of MCP-1 while enhancing apoptosis may serve as a potential therapeutic strategy to attenuate intimal hyperplasia.
Authors:
Yi Si; Jun Ren; Pu Wang; Debra L Rateri; Alan Daugherty; Xu-Dong Shi; K Craig Kent; Bo Liu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-02-09
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  32     ISSN:  1524-4636     ISO Abbreviation:  Arterioscler. Thromb. Vasc. Biol.     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-03-16     Completed Date:  2012-05-14     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  943-54     Citation Subset:  IM    
Affiliation:
Division of Vascular Surgery, University of Wisconsin Madison, 53705, USA.
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MeSH Terms
Descriptor/Qualifier:
Angioplasty, Balloon*
Animals
Antibodies / administration & dosage
Apoptosis
Carotid Artery Injuries / enzymology,  genetics,  immunology,  pathology,  therapy*
Cell Movement*
Cell Proliferation
Cells, Cultured
Chemokine CCL2 / antagonists & inhibitors,  immunology,  metabolism*
Connective Tissue / enzymology*,  immunology,  pathology
Culture Media, Conditioned / metabolism
Disease Models, Animal
Fibroblasts / enzymology*,  immunology,  pathology
Genetic Therapy*
Hyperplasia
Male
Muscle, Smooth, Vascular / enzymology*,  immunology,  pathology
Myocytes, Smooth Muscle / enzymology*,  immunology,  pathology
Protein Kinase C-delta / genetics,  metabolism*
Rats
Rats, Sprague-Dawley
Receptors, CCR2 / metabolism
Time Factors
Transfection
Grant Support
ID/Acronym/Agency:
R01 HL-81424/HL/NHLBI NIH HHS; R01 HL068673/HL/NHLBI NIH HHS; R01 HL081424/HL/NHLBI NIH HHS; R01 HL081424-04/HL/NHLBI NIH HHS; R01 HL081424-05/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies; 0/Ccl2 protein, rat; 0/Ccr2 protein, rat; 0/Chemokine CCL2; 0/Culture Media, Conditioned; 0/Receptors, CCR2; EC 2.7.11.13/Protein Kinase C-delta
Comments/Corrections

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


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