PMID- 26658094
OWN - NLM
STAT- MEDLINE
DCOM- 20170220
LR  - 20220321
IS  - 1873-3913 (Electronic)
IS  - 0898-6568 (Linking)
VI  - 28
IP  - 7
DP  - 2016 Jul
TI  - Adaptive phenotypic modulation of human arterial endothelial cells to fluid shear 
      stress-encoded signals: modulation by phosphodiesterase 4D-VE-cadherin 
      signalling.
PG  - 741-8
LID - S0898-6568(15)30007-3 [pii]
LID - 10.1016/j.cellsig.2015.12.001 [doi]
AB  - Although cAMP-signalling regulates numerous functions of vascular endothelial 
      cells (VECs), including their ability to impact vascular resistance in response 
      to changes in blood flow dynamics, few of the mechanisms underlying these effects 
      have yet to be described. In addition to forming stable adherens junctions (AJs) 
      in static VEC cultures, VE-cadherin (VECAD) has emerged as a critical component 
      in a key mechanosensor responsible for linking altered blood flow dynamics and 
      the VEC-mediated control of vascular resistance. Previously, a cAMP 
      phosphodiesterase, PDE4D, was shown to coordinate the VEC permeability limiting 
      effects of cAMP-elevating agents in human arterial VECs (HAECs). Herein, we 
      report that PDE4D acts to allow cAMP-elevating agents to regulate VECADs' role as 
      a sensor of flow-associated fluid shear stress (FSS)-encoded information in 
      HAECs. Thus, we report that PDE4 activity is increased in HAECs exposed to 
      laminar FSS and that this effect contributes to controlling how FSS impacts the 
      morphological and gene expression changes in HAECs exposed to flow. More 
      specifically, we report that PDE4D regulates the efficiency with which VECAD, 
      within its mechanosensor, controls VEGFR2 and Akt activities. Indeed, we show 
      that PDE4D knockdown (KD) significantly blunts responses of HAECs to levels of 
      FSS characteristically found in areas of the vasculature in which stenosis is 
      prevalent. We propose that this effect may provide a new therapeutic avenue in 
      modulating VEC behaviour at these sites by promoting an adaptive and 
      vasculo-protective phenotype.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Rampersad, Sarah N
AU  - Rampersad SN
AD  - Department of Pathology & Molecular Medicine, Queen's University, Kingston, ON, 
      Canada.
FAU - Wudwud, Alie
AU  - Wudwud A
AD  - Department of Pathology & Molecular Medicine, Queen's University, Kingston, ON, 
      Canada.
FAU - Hubert, Fabien
AU  - Hubert F
AD  - Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      ON, Canada.
FAU - Maurice, Donald H
AU  - Maurice DH
AD  - Department of Pathology & Molecular Medicine, Queen's University, Kingston, ON, 
      Canada; Department of Biomedical and Molecular Sciences, Queen's University, 
      Kingston, ON, Canada. Electronic address: mauriced@queensu.ca.
LA  - eng
GR  - MOP 114948/CIHR/Canada
GR  - MOP 57699/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151204
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Antigens, CD)
RN  - 0 (Cadherins)
RN  - 0 (Platelet Endothelial Cell Adhesion Molecule-1)
RN  - 0 (cadherin 5)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
RN  - EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 4)
RN  - EC 3.1.4.17 (PDE4D protein, human)
SB  - IM
MH  - Antigens, CD/*metabolism
MH  - Aorta/*cytology
MH  - Cadherins/*metabolism
MH  - Cell Shape
MH  - Cyclic AMP/metabolism
MH  - Cyclic Nucleotide Phosphodiesterases, Type 4/*metabolism
MH  - Endothelial Cells/*metabolism
MH  - Gene Expression Regulation
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Intercellular Junctions/metabolism
MH  - Mechanotransduction, Cellular
MH  - Phenotype
MH  - Platelet Endothelial Cell Adhesion Molecule-1/metabolism
MH  - *Shear Strength
MH  - *Signal Transduction
MH  - Vascular Endothelial Growth Factor Receptor-2/metabolism
OTO - NOTNLM
OT  - Fluid shear stress
OT  - Mechanosensor
OT  - Phosphodiesterase 4D
OT  - VE-cadherin
OT  - Vascular endothelial
EDAT- 2015/12/15 06:00
MHDA- 2015/12/15 06:01
CRDT- 2015/12/15 06:00
PHST- 2015/10/06 00:00 [received]
PHST- 2015/11/27 00:00 [revised]
PHST- 2015/12/01 00:00 [accepted]
PHST- 2015/12/15 06:00 [entrez]
PHST- 2015/12/15 06:00 [pubmed]
PHST- 2015/12/15 06:01 [medline]
AID - S0898-6568(15)30007-3 [pii]
AID - 10.1016/j.cellsig.2015.12.001 [doi]
PST - ppublish
SO  - Cell Signal. 2016 Jul;28(7):741-8. doi: 10.1016/j.cellsig.2015.12.001. Epub 2015 
      Dec 4.