[Blood flow sensing mechanism via calcium signaling in vascular endothelium].
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.
Department of Biomedical Engineering, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. k-yamanoto@umjn.ac.jp
Kimiko
K
Yamamoto
Joji
J
Ando
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology*; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D058848:Receptors, Purinergic P2X4 / Q000502:physiology; D012039:Regional Blood Flow / Q000502:physiology*; D013314:Stress, Mechanical
D058848:Receptors, Purinergic P2X4; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D002118:Calcium