scholarly journals STENT DEGRADATION OF NOVEL FULLY BIOABSORBABLE SALICYLATE-BASED SIROLIMUS-ELUTING STENT EVALUATED BY OCT IN PIG CORONARY ARTERY

2010 ◽  
Vol 55 (10) ◽  
pp. A217.E2058
Author(s):  
Daisuke Matsumoto ◽  
Toshiro Shinke ◽  
Sarah Geva ◽  
Nicolas Chronos ◽  
Refat Jabara
Keyword(s):  
Coronary Artery ◽  
Pig Coronary Artery ◽  
Sirolimus Eluting Stent

Abstract 604: Targeting Cx43 Prevents Growth Factor-Induced Phenotypic Change in Pig Coronary Artery Smooth Muscle Cells

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Christos E Chadjichristos ◽  
Sandrine Morel ◽  
Jean-Paul Derouette ◽  
Anne Brisset ◽  
Isabelle Roth ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Coronary Artery ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Phenotypic Change ◽  
Intimal Thickening ◽  
Cx43 Expression ◽  
Junction Protein ◽  
Pig Coronary Artery

Percutaneous coronary intervention (PCI) is commonly used to treat atherosclerotic coronary arteries, but its efficacy is limited by restenosis at the site of the intervention. We reported previously that reducing the expression of the gap junction protein connexin43 (Cx43) in mice restricted neointima formation after acute vascular injury by limiting the inflammatory response as well as the proliferation and migration of smooth muscle cells (SMCs) towards the damaged site. SMC populations isolated from the pig 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 intimal thickening. Here, we further investigate the relationship between connexin expression and SMC phenotype using the distinct types of pig coronary artery SMCs. We show that Cx40 was highly expressed in normal media of porcine coronary artery in vivo, whereas Cx43 was barely detectable. In contrast, Cx40 was down-regulated and Cx43 was markedly up-regulated in SMCs of stent-induced intimal thickening. In vitro, S-SMCs expressed Cx40 and Cx43. Cx43 expression was increased in R-SMCs and these cells no longer expressed Cx40. When S-SMCs were treated with 10 ng/ml platelet-derived growth factor (PDGF-BB) they acquired a rhomboid phenotype and their migratory activity increased (from 40.3±5.7 to 185.9±27.3 migrating cells; mean±SEM, N=4, P<0.01). These changes were accompanied by an increase in Cx43 and loss of Cx40 expression. Importantly, PDGF-BB-induced phenotypic change of S-SMCs was prevented by reducing Cx43 expression with 100 uM antisense for Cx43. Thus, Cx43 antisense-treated SMCs retained their typical elongated appearance and the expression of some SMC differentiation markers, such as alpha-SM actin, whereas the appearance of S100A4, a typical marker of R-SMCs, was prevented. In conclusion, limiting Cx43 expression in SMCs prevents growth factor-induced changes towards a deleterious phenotype. Our findings suggest that Cx43 might be an additional target for local delivery strategies aimed at reducing restenosis after PCI.

Estrogen reduces proliferation and agonist-induced calcium increase in coronary artery smooth muscle cells

1997 ◽  
Vol 272 (4) ◽  
pp. H1996-H2003 ◽  
Author(s):  
R. C. Bhalla ◽  
K. F. Toth ◽  
R. A. Bhatty ◽  
L. P. Thompson ◽  
R. V. Sharma
Keyword(s):  
Cell Proliferation ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Guinea Pig ◽  
Untreated Control ◽  
Fetal Calf Serum ◽  
Thymidine Incorporation ◽  
Calf Serum ◽  
Causative Role ◽  
Pig Coronary Artery

Epidemiological evidence and estrogen replacement studies suggest that estrogen has a protective effect on the cardiovascular system against coronary artery disease. Vascular smooth muscle (VSM) cell replication has been shown to play a causative role in the pathogenesis of atherosclerosis. Therefore, in this study, we investigated the effect of chronic treatment of cultured guinea pig coronary artery VSM cells with physiological concentrations of 17beta-estradiol (E2) on thymidine incorporation, cell proliferation, and bradykinin-stimulated cytosolic calcium concentration ([Ca2+]i). Bradykinin at physiological concentrations causes contraction of endothelium-denuded guinea pig coronary artery rings in a concentration-dependent manner. VSM cells were first treated with low doses of E2 (10 pg/ml) for 1-2 days followed by treatment for 4-6 days with 50 pg/ml of E2, a concentration similar to that found in pregnancy. Using these protocols, we consistently observed the presence of E2-receptor mRNA in VSM cells by a ribonuclease protection assay. Fetal calf serum-stimulated [3H]thymidine incorporation was significantly reduced (P < 0.05) in E2-treated cells compared with untreated control cells. Similarly, E2 treatment significantly inhibited fetal calf serum-stimulated VSM cell proliferation compared with untreated control cells (P < 0.05). We also tested the hypothesis that E2 treatment attenuates agonist-stimulated [Ca2+]i in VSM cells because acute E2 treatment has been shown to produce relaxation of precontracted isolated coronary artery preparations. E2 treatment of VSM cells resulted in a significant decrease in bradykinin-stimulated [Ca2+]i compared with untreated cells (P < 0.05). In conclusion, our data demonstrate that estrogen at physiological concentrations directly regulates coronary VSM cell function.

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