Document Detail


[Blood flow sensing mechanism via calcium signaling in vascular endothelium].
MedLine Citation:
PMID:  21048396     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
The structure and function of blood vessels adapt to environmental changes, for example, physical development and exercise. This phenomenon is based on the ability of endothelial cells (ECs) to sense and respond to blood flow. ECs are in direct contact with blood flow and exposed to shear stress. A number of recent studies have revealed that ECs recognize changes in shear stress and transmit signals to the interior of the cell, which leads to cellular responses that involve changes in cell morphology, cell function, and gene expression. Cultured human pulmonary artery ECs (HPAECs) showed Ca²(+) influx via an ATP-operated cation channel, P2X4, in response to shear stress. We have recently found that shear-induced activation of P2X4 requires endogenously released ATP and that shear stress induced HPAECs to release ATP, which was mediated by cell-surface ATP synthase located in caveolae. To gain insight into its significance, we generated a P2X4-deficient mouse. P2X4(-/-) mice do not exhibit normal EC responses to flow, such as Ca²(+) influx and subsequent production of NO, a potent vasodilator. Additionally, vessel dilation induced by acute increases in blood flow is markedly suppressed in P2X4(-/-) mice. Furthermore, P2X4(-/-) mice have higher blood pressure than wild-type mice. Moreover, no adaptive vascular remodeling is observed in the P2X4(-/-) mice. Thus, P2X4-mediated shear stress mechanotransduction plays an important role in the vascular homeostasis, including the control of blood pressure and vascular remodeling.
Authors:
Kimiko Yamamoto; Joji Ando
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Publication Detail:
Type:  English Abstract; Journal Article    
Journal Detail:
Title:  Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan     Volume:  130     ISSN:  0031-6903     ISO Abbreviation:  Yakugaku Zasshi     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-04     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0413613     Medline TA:  Yakugaku Zasshi     Country:  Japan    
Other Details:
Languages:  jpn     Pagination:  1407-11     Citation Subset:  IM    
Affiliation:
Department of Biomedical Engineering, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. k-yamanoto@umjn.ac.jp
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