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Development of vascular smooth muscle contractility by endothelium-derived transforming growth factor β proteins

  • Signaling and cell physiology
  • Published:
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Abstract

It is well established that the release of vasodilators and vasoconstrictors from vascular endothelium regulates vascular smooth muscle contraction. In this report, we investigate the role of the endothelium in the development and maintenance of constitutive vascular contractility. For that purpose, contractile activity of cultured bovine aortic smooth muscle cells (BASMCs) embedded in collagen gels was monitored by changes in gel diameter. After culturing for 5 days, ATP- and high KCl solution-induced contractions were significantly enhanced in the gels that were overlaid with bovine aortic endothelial cells (BAECs) or were cultured with conditioned medium of cultured BAECs. ATP-induced Ca2+ transients, recorded in BASMCs cultured with conditioned medium of BAECs, were markedly augmented, but high KCl-induced Ca2+ transients were not affected. BASMCs in control gels were spindle shaped, and those in endothelium-treated gels were more elongated and interconnected. The endothelial conditioned medium also strongly affected the intracellular distribution of actin fibers. Conditioned medium of BAECs contained TGFβ1 and TGFβ2. The TGFβ receptor antagonist SB431542 as well as simultaneous treatment with TGFβ1 and TGFβ2 neutralizing antibodies completely reversed the above effects of endothelial conditioned medium on BASMCs. BAECs medium induced phosphorylation of Smad2 and increased ATP-induced phosphorylation of myosin light chain in BASMCs. The present results indicate that the release of TGFβ1 and TGFβ2 from vascular endothelium affects the contractility of vascular smooth muscle cells by altering their morphology and agonist-induced Ca2+ mobilization.

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Acknowledgments

The authors thank Dr. Guy Droogmans for kindly reading the manuscript.

This work was supported by JSPS KAKENHI Grant Number 25670129.

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Authors and Affiliations

  1. Department of Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan

    Chiwaka Kimura, Shuhei Konishi, Maki Hasegawa & Masahiro Oike

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  1. Chiwaka Kimura
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  2. Shuhei Konishi
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  4. Masahiro Oike
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Correspondence to Masahiro Oike.

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Kimura, C., Konishi, S., Hasegawa, M. et al. Development of vascular smooth muscle contractility by endothelium-derived transforming growth factor β proteins. Pflugers Arch - Eur J Physiol 466, 369–380 (2014). https://doi.org/10.1007/s00424-013-1329-6

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  • DOI: https://doi.org/10.1007/s00424-013-1329-6

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