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Shear stress-induced upregulation of connexin 43 expression in endothelial cells on upstream surfaces of rat cardiac valves

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Abstract

Endothelial expression of the gap junction proteins, connexin (Cx) 37, Cx40, and Cx43, varies within the vascular network. While previous studies suggest that shear stress may upregulate Cx43, it is not well understood if shear stress affects the expression of all endothelial connexins and to what extent. Endothelial cells on the upstream and downstream surfaces of cardiac valves are subjected to considerably different intensities of shear stress. We therefore reasoned that we could determine the extent hemodynamic forces affect the expression of Cx37, Cx40, and Cx43 by comparing their immunohistochemical distribution on the upstream and downstream surfaces of rat cardiac valves. We found 70- to 200-fold greater expression of Cx43 in the endothelial cells on the upstream than on the downstream surfaces. However, Cx37 was expressed almost equally in the endothelial cells on upstream and downstream surfaces, and Cx40, a major connexin in most vascular endothelial cells, was not detected on either surface. In addition to the heterogeneity in Cx43 expression, endothelial cells on the upstream surface were 35% to 65% smaller than those on the corresponding downstream surface. These results suggest that shear stress may affect endothelial cell size and Cx43 expression but not Cx37 expression.

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Acknowledgements

This work was supported in part by grants from Koga Hideya Funds, Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Culture, Japan (numbers 08770015, 09770010, 11770008, and 16590146), and the National Institutes of Health (grants HL-24136 and HL-59157 from the National, Heart, Lung, and Blood Institute and P50-CA90270 from the National Cancer Institute).

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Authors and Affiliations

  1. Department of Developmental Molecular Anatomy, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, 812-8582, Fukuoka, Japan

    Tetsuichiro Inai & Yosaburo Shibata

  2. Cardiovascular Research Institute, Comprehensive Cancer Center, and Department of Anatomy, University of California, San Francisco, CA 94143, USA

    Michael R. Mancuso & Donald M. McDonald

  3. Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Junichi Kobayashi & Kyoko Nakamura

Authors
  1. Tetsuichiro Inai
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  2. Michael R. Mancuso
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  3. Donald M. McDonald
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  4. Junichi Kobayashi
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  5. Kyoko Nakamura
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  6. Yosaburo Shibata
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Correspondence to Tetsuichiro Inai.

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Inai, T., Mancuso, M.R., McDonald, D.M. et al. Shear stress-induced upregulation of connexin 43 expression in endothelial cells on upstream surfaces of rat cardiac valves. Histochem Cell Biol 122, 477–483 (2000). https://doi.org/10.1007/s00418-004-0717-6

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