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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook 2016     Display Documents

ID: 723909.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook 2016
P2Y(2) and Gq/G(1)(1) control blood pressure by mediating endothelial mechanotransduction
Authors:Wang, S.; Iring, A.; Strilic, B.; Albarran Juarez, J.; Kaur, H.; Troidl, K.; Tonack, S.; Burbiel, J. C.; Muller, C. E.; Fleming, I.; Lundberg, J. O.; Wettschureck, N.; Offermanns, S.
Date of Publication (YYYY-MM-DD):2015-08-03
Title of Journal:J Clin Invest
Issue / Number:8
Start Page:3077
End Page:3086
Audience:Not Specified
Abstract / Description:Elevated blood pressure is a key risk factor for developing cardiovascular diseases. Blood pressure is largely determined by vasodilatory mediators, such as nitric oxide (NO), that are released from the endothelium in response to fluid shear stress exerted by the flowing blood. Previous work has identified several mechanotransduction signaling processes that are involved in fluid shear stress-induced endothelial effects, but how fluid shear stress initiates the response is poorly understood. Here, we evaluated human and bovine endothelial cells and found that the purinergic receptor P2Y2 and the G proteins Gq/G11 mediate fluid shear stress-induced endothelial responses, including [Ca2+]i transients, activation of the endothelial NO synthase (eNOS), phosphorylation of PECAM-1 and VEGFR-2, as well as activation of SRC and AKT. In response to fluid shear stress, endothelial cells released ATP, which activates the purinergic P2Y2 receptor. Mice with induced endothelium-specific P2Y2 or Gq/G11 deficiency lacked flow-induced vasodilation and developed hypertension that was accompanied by reduced eNOS activation. Together, our data identify P2Y2 and Gq/G11 as a critical endothelial mechanosignaling pathway that is upstream of previously described mechanotransduction processes and demonstrate that P2Y2 and Gq/G11 are required for basal endothelial NO formation, vascular tone, and blood pressure.
Free Keywords:Animals; Blood Pressure/*physiology; Calcium Signaling/*physiology; Cattle; GTP-Binding Protein alpha Subunits, Gq-G11/genetics/*metabolism; Human Umbilical Vein Endothelial Cells/cytology/*metabolism; Humans; Hypertension/genetics/metabolism/pathology; Mechanotransduction, Cellular/*physiology; Mice; Mice, Knockout; Nitric Oxide/genetics/metabolism; Nitric Oxide Synthase Type III/genetics/metabolism; Receptors, Purinergic P2Y2/genetics/*metabolism; Vascular Endothelial Growth Factor Receptor-2/genetics/metabolism; Vasodilation/physiology
External Publication Status:published
Document Type:Article
Communicated by:n.n.
Affiliations:MPI für physiologische und klinische Forschung
Identifiers:ISSN:1558-8238 (Electronic) 0021-9738 (Linking) %R 10.1172/JCI81067
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