Journal of Zhejiang University SCIENCE B

, Volume 7, Issue 8, pp 648–653 | Cite as

Effects of angiotensin II on connexin 43 of VSMCs in arteriosclerosis

  • Cai Wei 
  • Ruan Li-ming 
  • Wang Yi-na 
  • Chen Jun-zhu 
Article

Abstract

Objective: To observe the effect of angiotensin II (Ang II) on expression of gap junction channel protein connexin 43 (Cx43) in the proliferation process of vascular smooth muscle cells (VSMCs) during the early stage of arteriosclerosis. Methods: Thirty-two adult male rabbits were randomly divided into 4 groups. Rabbits in Group A were fed common diet while others in Groups B, C, and D were fed high-cholesterol diet. Losartan (10 mg/(kg·d)) and ramipril (0.5 mg/(kg·d)) were added in the diet of Groups C and D, respectively. The animals were sacrificed after 8 weeks and abdominal aortas were removed and dissected. The expression of Cx43 was assayed using RT-PCR and Western Blotting analysis. Results: Cx43 was increased markedly in both protein and mRNA level in Groups B, C, and D fed high-cholesterol diet compared with that in control group (P<0.01). Cx43 level in losartan or ramipril treated groups was higher than that in control group (P<0.01, P<0.05), but lower than that in high-cholesterol diet groups (P<0.05, P<0.01). Conclusion: Cx43 level was upregulated in VSMCs during early atherosclerosis. Losartan and ramipril can inhibit the expression of Cx43.

Key words

Atherosclerosis Connexin mRNA Losartan Ramipril 

CLC number

R331 

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References

  1. Beyer, E.C., 1993. Gap junctions. Int. Rev. Cytol., 137C:1–37.PubMedGoogle Scholar
  2. Blackburn, J.P., Peters, N.S., Yeh, H.I., Rothery, S., Green, C.R., Severs, N.J., 1995. Upregulation of connexin 43 gap junctions during early stages of human coronary atherosclerosis. Arterioscler. Thromb. Vasc. Biol., 15(8):219–228.Google Scholar
  3. Bokkala, S., Reis, H.M., Rubin, E., Joseph, S.K., 2001. Effect of angiotensin II and ethanol on the expression of connexin 43 in WB rat liver epithelial cells. Biochem. J., 357(3):769–777. [doi:10.1042/0264-6021:3570769]PubMedCrossRefGoogle Scholar
  4. Dodge, S.M., Beardslee, M.A., Darrow, B.J., Green, K.G., Beyer, E.C., Saffitz, J.E., 1998. Effects of angiotensin II on expression of the gap junction channel protein connexin43 in neonatal rat ventricular myocytes. J. Am. Coll. Cardiol., 32(3):800–807. [doi:10.1016/S0735-1097(98)00317-9]PubMedCrossRefGoogle Scholar
  5. Emdad, L., Uzzaman, M., Takagishi, Y., Honjo, H., Uchida, T., Severs, N.J., Kodama, I., Murata, Y., 2001. Gap junction remodeling in hypertrophied left ventricles of aortic-banded rats: prevention by angiotensin type 1 receptor blockade. J. Mol. Cell. Cardiol., 33(2):219–213. [doi:10.1006/jmcc.2000.1293]PubMedCrossRefGoogle Scholar
  6. Inoguchi, T., Ueda, F., Umeda, F., Yamashita, T., Nawata, H., 1995. Inhibition of intercellular communication via gap junction in cultured aortic endothelial cells by elevated glucose and phorbol ester. Biochem. Biophys. Res. Commun., 208(2):492–497. [doi:10.1006/bbrc.1995.1365]PubMedCrossRefGoogle Scholar
  7. Kwak, B.R., Veillard, N., Pelli, G., Mulhaupt, F., James, R.W., Chanson, M., Mach, F., 2003. Reduced connexin43 expression inhibits atherosclerotic lesion formation in low-density lipoprotein receptor-deficient mice. Circulation, 107(7):1033–1039. [doi:10.1161/01.CIR.0000051364.70064.D1]PubMedCrossRefGoogle Scholar
  8. Li, X., Simardm, J.M., 1999. Multiple connexins form gap junction channels in rat basilar artery smooth muscle cells. Circ. Res., 84(11):1277–1284.PubMedGoogle Scholar
  9. Li, J., Hirose, N., Kawamura, M., Arai, Y., 1999. Antiatherogenic effect of angiotensin converting enzyme inhibitor and angiotensin II receptor antagonist in the cholesterol-fed rabbits. Atherosclerosis, 143(2):315–326. [doi:10.1016/S0021-9150(98)00309-8]PubMedCrossRefGoogle Scholar
  10. Lin, J.H., Yang, J., Liu, S., Takano, T., Wang, X., Gao, Q., Willecke, K., Nedergaard, M., 2003. Connexin in mediates gap junction-independent resistance to cellular injury. J. Neurosci., 23(2):430–441.PubMedGoogle Scholar
  11. Mensink, A., de Haan, L.H., Lakemond, C.M., Koelman, C.A., Koeman, J.H., 1995. Inhibition of gap junctional intercellular communication between primary human smooth muscle cells by tumor necrosis factor alpha. Carcinogenesis, 16(9):2063–2067.PubMedGoogle Scholar
  12. Mensink, A., Brouwer, A., van den Burg, E.H., Geurts, S., Jongen, W.M., Lakemond, C.M., Meijerman, I., van der Wijk, T., 1996. Modulation of intercellular communication between smooth muscle cells by growth factors and cytokines. Eur. J. Pharmacol., 310(1):73–81. [doi:10.1016/0014-2999(96)00368-8]PubMedCrossRefGoogle Scholar
  13. Polacek, D., Bech, F., McKinsey, J.F., Davies, P.F., 1997. Connexin43 gene expression in the rabbit arterial wall: effects of hypercholesterolemia, balloon injury and their combination. J. Vasc. Res., 34(2):10–30.Google Scholar
  14. Polontchouk, L., Ebelt, B., Jackels, M., Dhein, S., 2002. Chronic effects of endothelin-1 and angiotensin II on gap junctions and intercellular communication in cardiac cells. FASEB J., 16(1):87–89.PubMedGoogle Scholar
  15. Saltis, J., Thomas, A.C., Agrotis, A., Campbell, J.H., Campbell, G.R., Bobik, A., 1995. Expression of growth factor receptors in arterial smooth muscle cells. Dependency on cell phenotype and serum factors. Atherosclerosis, 118(1):77–87. [doi:10.1016/0021-9150(95)05595-N]PubMedCrossRefGoogle Scholar
  16. Sandow, S.L., Tare, M., Coleman, H.A., Hill, C.E., Parkington, H.C., 2002. Involvement of myoendothelial gap junctions in the actions of endothelium-derived hyperpolarizing factor. Circ. Res., 90(10):1108–1113. [doi:10.1161/01.RES.0000019756.88731.83]PubMedCrossRefGoogle Scholar
  17. Schmidt-Ott, K.M., Kagiyama, S., Phillips, M.I., 2000. The multiple actions of angiotensin II in atherosclerosis. Regulatory Peptides, 93(1–3):65–77. [doi:10.1016/S01670115(00)00178-6]PubMedCrossRefGoogle Scholar
  18. Shyu, K.G., Chen, C.C., Wang, B.W., Kuan, P., 2001. Angiotensin II receptor antagonist blocks the expression of connexin43 induced by cyclical mechanical stretch in cultured neonatal rat cardiac myocytes. J. Mol. Cell Cardiol., 33(4):691–698. [doi:10.1006/jmcc.2000.1333]PubMedCrossRefGoogle Scholar

Copyright information

© Zhejiang University 2006

Authors and Affiliations

  • Cai Wei 
    • 1
  • Ruan Li-ming 
    • 1
  • Wang Yi-na 
    • 1
  • Chen Jun-zhu 
    • 1
  1. 1.Department of Internal Medicine, the First Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina

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