Abstract
Background: Changes in connexin expression have been found in vascular smooth muscle cells (VSMCs) during the progression of atherosclerotic lesion and intimal hyperplasia. It is our hypothesis that increased connexin43 expression following stimulation of VSMCs with Ang II and IGF-1 contributes to more proliferation in saphenous vein (SV) than in the internal mammary artery (IMA). Materials and method: Using immunohistochemistry, Western blot, and reverse-transcription polymerase chain reaction, we assessed the effect of Ang II and IGF-1 stimulation on connexin43 expression and the signaling pathways involved in VSMCs of SV and IMA. Results: Immunostaining demonstrated strong expression of connexin43 in SV compared with IMA after stimulation with Ang II and IGF-1. Ang II up-regulated the expression of connexin43 in VSMCs of SV in a dose- and time-dependent manner. This was inhibited by p38 and ERK MAP kinase inhibitors, SB203580 and PD98059, respectively. In the VSMCs of IMA, the connexin43 expression was markedly low and maintained at a reduced level even after 3 h stimulation. IGF-1 dose-dependently induced mRNA expression of connexin43 in the VSMCs of SV, which was blocked by PD98059. However, in VSMCs of IMA there was no significant effect of IGF-1 on the connexin43 mRNA expression. Conclusion: These data suggest that connexin43 expression can be influenced by Ang II and IGF-1 through ERK and p38 pathways and may contribute to the pathogenesis of vein graft disease following coronary artery bypass grafting.
| Original language | English |
|---|---|
| Pages (from-to) | 137-142 |
| Number of pages | 6 |
| Journal | Journal of Surgical Research |
| Volume | 142 |
| Issue number | 1 |
| DOIs | |
| State | Published - Sep 2007 |
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All Science Journal Classification (ASJC) codes
- Surgery
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Angiotensin II and IGF-1 Regulate Connexin43 Expression Via ERK and p38 Signaling Pathways in Vascular Smooth Muscle Cells of Coronary Artery Bypass Conduits. / Jia, Guanghong; Mitra, Amit K.; Cheng, Gang; Gangahar, Deepak M.; Agrawal, Devendra K.
In: Journal of Surgical Research, Vol. 142, No. 1, 09.2007, p. 137-142.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Angiotensin II and IGF-1 Regulate Connexin43 Expression Via ERK and p38 Signaling Pathways in Vascular Smooth Muscle Cells of Coronary Artery Bypass Conduits
AU - Jia, Guanghong
AU - Mitra, Amit K.
AU - Cheng, Gang
AU - Gangahar, Deepak M.
AU - Agrawal, Devendra K.
PY - 2007/9
Y1 - 2007/9
N2 - Background: Changes in connexin expression have been found in vascular smooth muscle cells (VSMCs) during the progression of atherosclerotic lesion and intimal hyperplasia. It is our hypothesis that increased connexin43 expression following stimulation of VSMCs with Ang II and IGF-1 contributes to more proliferation in saphenous vein (SV) than in the internal mammary artery (IMA). Materials and method: Using immunohistochemistry, Western blot, and reverse-transcription polymerase chain reaction, we assessed the effect of Ang II and IGF-1 stimulation on connexin43 expression and the signaling pathways involved in VSMCs of SV and IMA. Results: Immunostaining demonstrated strong expression of connexin43 in SV compared with IMA after stimulation with Ang II and IGF-1. Ang II up-regulated the expression of connexin43 in VSMCs of SV in a dose- and time-dependent manner. This was inhibited by p38 and ERK MAP kinase inhibitors, SB203580 and PD98059, respectively. In the VSMCs of IMA, the connexin43 expression was markedly low and maintained at a reduced level even after 3 h stimulation. IGF-1 dose-dependently induced mRNA expression of connexin43 in the VSMCs of SV, which was blocked by PD98059. However, in VSMCs of IMA there was no significant effect of IGF-1 on the connexin43 mRNA expression. Conclusion: These data suggest that connexin43 expression can be influenced by Ang II and IGF-1 through ERK and p38 pathways and may contribute to the pathogenesis of vein graft disease following coronary artery bypass grafting.
AB - Background: Changes in connexin expression have been found in vascular smooth muscle cells (VSMCs) during the progression of atherosclerotic lesion and intimal hyperplasia. It is our hypothesis that increased connexin43 expression following stimulation of VSMCs with Ang II and IGF-1 contributes to more proliferation in saphenous vein (SV) than in the internal mammary artery (IMA). Materials and method: Using immunohistochemistry, Western blot, and reverse-transcription polymerase chain reaction, we assessed the effect of Ang II and IGF-1 stimulation on connexin43 expression and the signaling pathways involved in VSMCs of SV and IMA. Results: Immunostaining demonstrated strong expression of connexin43 in SV compared with IMA after stimulation with Ang II and IGF-1. Ang II up-regulated the expression of connexin43 in VSMCs of SV in a dose- and time-dependent manner. This was inhibited by p38 and ERK MAP kinase inhibitors, SB203580 and PD98059, respectively. In the VSMCs of IMA, the connexin43 expression was markedly low and maintained at a reduced level even after 3 h stimulation. IGF-1 dose-dependently induced mRNA expression of connexin43 in the VSMCs of SV, which was blocked by PD98059. However, in VSMCs of IMA there was no significant effect of IGF-1 on the connexin43 mRNA expression. Conclusion: These data suggest that connexin43 expression can be influenced by Ang II and IGF-1 through ERK and p38 pathways and may contribute to the pathogenesis of vein graft disease following coronary artery bypass grafting.
UR - http://www.scopus.com/inward/record.url?scp=34547940871&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34547940871&partnerID=8YFLogxK
U2 - 10.1016/j.jss.2006.11.007
DO - 10.1016/j.jss.2006.11.007
M3 - Article
VL - 142
SP - 137
EP - 142
JO - Journal of Surgical Research
JF - Journal of Surgical Research
SN - 0022-4804
IS - 1
ER -