Angiotensin II and IGF-1 Regulate Connexin43 Expression Via ERK and p38 Signaling Pathways in Vascular Smooth Muscle Cells of Coronary Artery Bypass Conduits

Guanghong Jia, Amit K. Mitra, Gang Cheng, Deepak M. Gangahar, Devendra K. Agrawal

Research output: Contribution to journalArticle

23 Citations (Scopus)

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 languageEnglish
Pages (from-to)137-142
Number of pages6
JournalJournal of Surgical Research
Volume142
Issue number1
DOIs
StatePublished - Sep 2007

Fingerprint

Connexin 43
Insulin-Like Growth Factor I
Vascular Smooth Muscle
Coronary Artery Bypass
Angiotensin II
Smooth Muscle Myocytes
Mammary Arteries
Saphenous Vein
Tunica Intima
Messenger RNA
Connexins
MAP Kinase Signaling System
Extracellular Signal-Regulated MAP Kinases
p38 Mitogen-Activated Protein Kinases
Reverse Transcription
Hyperplasia
Veins
Western Blotting
Immunohistochemistry
Transplants

All Science Journal Classification (ASJC) codes

  • Surgery

Cite this

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 journalArticle

@article{8091ca624709492eb9090cec1ccfc458,
title = "Angiotensin II and IGF-1 Regulate Connexin43 Expression Via ERK and p38 Signaling Pathways in Vascular Smooth Muscle Cells of Coronary Artery Bypass Conduits",
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.",
author = "Guanghong Jia and Mitra, {Amit K.} and Gang Cheng and Gangahar, {Deepak M.} and Agrawal, {Devendra K.}",
year = "2007",
month = "9",
doi = "10.1016/j.jss.2006.11.007",
language = "English",
volume = "142",
pages = "137--142",
journal = "Journal of Surgical Research",
issn = "0022-4804",
publisher = "Academic Press Inc.",
number = "1",

}

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 -