|Targeting connexin 43 prevents platelet-derived growth factor-BB-induced phenotypic change in porcine coronary artery smooth muscle cells.|
|PMID: 18239136 Owner: NLM Status: MEDLINE|
|We previously reported that reducing the expression of the gap junction protein connexin (Cx)43 in mice restricts intimal thickening formation after acute vascular injury by limiting the inflammatory response and the proliferation and migration of smooth muscle cells (SMCs) toward the damaged site. SMC populations isolated from porcine coronary artery exhibit distinct phenotypes: spindle-shaped (S) and rhomboid (R). S-SMCs are predominant in the normal media, whereas R-SMCs are recovered in higher proportion from stent-induced intimal thickening, suggesting that they participate in the restenotic process. Here, we further investigate the relationship between connexin expression and SMC phenotypes using porcine coronary artery SMCs. Cx40 was highly expressed in normal media of porcine coronary artery in vivo, whereas Cx43 was barely detectable. In contrast, Cx40 was downregulated and Cx43 was markedly upregulated in stent-induced intimal thickening. In vitro, S-SMCs expressed Cx40 and Cx43. In R-SMCs, Cx43 expression was increased and Cx40 was absent. We confirmed that S-SMCs treated with platelet-derived growth factor-BB acquire an R phenotype. This was accompanied by an upregulation of Cx43 and a loss of Cx40. Importantly, platelet-derived growth factor-BB-induced S-to-R phenotypic change was prevented by a reduction of Cx43 expression with antisense, ie, S-SMCs retained their typical elongated appearance and the expression of alpha-smooth muscle actin, a well-known SMC differentiation marker, whereas the expression of S100A4, a typical marker of R-SMCs, was prevented. In conclusion, limiting Cx43 expression in S-SMCs prevents platelet-derived growth factor-BB-induced S-to-R modulation. This suggests that Cx43 may be an additional target for local delivery strategies aimed at reducing restenosis.|
|Christos E Chadjichristos; Sandrine Morel; Jean-Paul Derouette; Esther Sutter; Isabelle Roth; Anne C Brisset; Marie-Luce Bochaton-Piallat; Brenda R Kwak|
Related Documents :
|9873066 - Cyclic nucleotide regulation of pai-1 mrna stability. identification of cytosolic prote...
9045716 - Low density lipoprotein receptor-related protein modulates the expression of tissue-typ...
10066866 - Nicotine increases plasminogen activator inhibitor-1 production by human brain endothel...
4039726 - Induction of fibrinolytic activity in hela cells by phorbol myristate acetate. tissue-t...
16051526 - A non-lethal method to estimate cyp1a expression in laboratory and wild atlantic salmon...
9644206 - Interaction of mitochondrial rna editing and nucleolytic processing in the restoration ...
|Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-01-31|
|Title: Circulation research Volume: 102 ISSN: 1524-4571 ISO Abbreviation: Circ. Res. Publication Date: 2008 Mar|
|Created Date: 2008-03-28 Completed Date: 2008-04-10 Revised Date: -|
Medline Journal Info:
|Nlm Unique ID: 0047103 Medline TA: Circ Res Country: United States|
|Languages: eng Pagination: 653-60 Citation Subset: IM|
|Division of Cardiology, Geneva University Hospitals, Faculty of Medicine, University of Geneva, Switzerland.|
|APA/MLA Format Download EndNote Download BibTex|
Connexin 43 / antagonists & inhibitors, genetics, metabolism*
Connexins / metabolism
Coronary Stenosis / etiology, metabolism*, pathology
Coronary Vessels / metabolism, pathology
Disease Models, Animal
Gap Junctions / drug effects, metabolism
Glycyrrhetinic Acid / analogs & derivatives, pharmacology
Muscle, Smooth, Vascular / drug effects, metabolism*, pathology
Myocytes, Smooth Muscle / drug effects, metabolism*, pathology
Peptides / pharmacology
Platelet-Derived Growth Factor / metabolism*
RNA, Small Interfering / metabolism
Recombinant Proteins / metabolism
S100 Proteins / metabolism
Signal Transduction* / drug effects
Stents / adverse effects
Tunica Intima / metabolism, pathology
|0/Actins; 0/Connexin 43; 0/Connexins; 0/Peptides; 0/Platelet-Derived Growth Factor; 0/RNA, Small Interfering; 0/Recombinant Proteins; 0/S100 Proteins; 0/connexin 40; 0/platelet-derived growth factor BB; 1449-05-4/18alpha-glycyrrhetinic acid; 471-53-4/Glycyrrhetinic Acid|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Cellular and molecular aspects of ovarian follicle ageing.
Next Document: Hairy-related transcription factors inhibit Notch-induced smooth muscle alpha-actin expression by in...