Abstract
Vascular endothelial cells (ECs) change their morphology, function, and gene expression in response to shear stress, a fluid mechanical force generated by flowing blood. This fact suggests that ECs recognize shear stress and transmit signals to the interior of the cell. Shear-stress-sensing and response mechanisms, however, have not been fully understood. We have demonstrated that ECs are capable of converting information regarding shear stress intensity into changes in intracellular Ca2+ concentration. The Ca2+ signaling is based on cell-surface ATP synthase-mediated ATP release and subsequent activation of an ATP-operated cation channel P2X4, which leads to a Ca2+ influx. Our studies using P2X4-deficient mice revealed that P2X4-mediated Ca2+ signaling of shear stress plays a crucial role in the homeostasis of the circulatory system, including the control of blood pressure, blood-flow-dependent vasodilation, and vascular remodeling, through endothelial nitric oxide production.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Korenaga R, Ando J, Tsuboi H et al (1994) Laminar flow stimulates ATP- and shear stress-dependent nitric oxide production in cultured bovine endothelial cells. Biochem Biophys Res Commun 198:213–219
Takada Y, Shinkai F, Kondo S et al (1994) Fluid shear stress increases the expression of thrombomodulin by cultured human endothelial cells. Biochem Biophys Res Commun 205:1345–1352
Davies PF (1995) Flow-mediated endothelial mechanotransduction. Physiol Rev 75:519–560
Korenaga R, Ando J, Kosaki K et al (1997) Negative transcriptional regulation of the VCAM-1 gene by fluid shear stress in murine endothelial cells. Am J Physiol 273:C1506–C1515
Kosaki K, Ando J, Korenaga R et al (1998) Fluid shear stress increases the production of granulocyte-macrophage colony-stimulating factor by endothelial cells via mRNA stabilization. Circ Res 82:794–802
Ando J, Korenaga R, Kamiya A (1999) Flow-induced endothelial gene regulation. In: Lelkes PI (ed) Mechanical Forces and the Endothelium. Harwood Academic Publishers, London, pp 111–126
Ohura N, Yamamoto K, Ichioka S et al (2003) Global analysis of shear stress-responsive genes in vascular endothelial cells. J Atheroscler Thromb 10:304–313
Ando J, Komatsuta T, Kamiya A (1988) Cytoplasmic calcium response to fluid shear stress in cultured vascular endothelial cells. In Vitro Cell Dev Biol 24:871–877
Ando J, Ohtsuka A, Korenaga R et al (1993) Wall shear stress rather than shear rate regulates cytoplasmic Ca2+ responses to flow in vascular endothelial cells. Biochem Biophys Res Commun 190:716–723
Yamamoto K, Korenaga R, Kamiya A et al (2000) P2X4 receptors mediate ATP-induced calcium influx in human vascular endothelial cells. Am J Physiol Heart Circ Physiol 279:H285–H292
Yamamoto K, Korenaga R, Kamiya A et al (2000) Fluid shear stress activates Ca2+ influx into human endothelial cells via P2X4 purinoceptors. Circ Res 87:385–391
Yamamoto K, Sokabe T, Ohura N et al (2003) Endogenously released ATP mediates shear stress-induced Ca2+ influx into pulmonary artery endothelial cells. Am J Physiol Heart Circ Physiol 285:H793–H803
Yamamoto K, Shimizu N, Obi S et al (2007) Involvement of cell surface ATP synthase in flow-induced ATP release by vascular endothelial cells. Am J Physiol Heart Circ Physiol 293:H1646–H1653
Yamamoto K, Sokabe T, Matsumoto T et al (2006) Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice. Nat Med 12:133–137
Rudic RD, Shesely EG, Maeda N et al (1998) Direct evidence for the importance of endothelium-derived nitric oxide in vascular remodeling. J Clin Invest 101:731–736
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer
About this paper
Cite this paper
Ando, J., Yamamoto, K. (2010). Shear-stress-sensing and response mechanisms in vascular endothelial cells. In: Sasano, T., Suzuki, O. (eds) Interface Oral Health Science 2009. Springer, Tokyo. https://doi.org/10.1007/978-4-431-99644-6_1
Download citation
DOI: https://doi.org/10.1007/978-4-431-99644-6_1
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-99643-9
Online ISBN: 978-4-431-99644-6
eBook Packages: MedicineMedicine (R0)