PMID- 24368096
OWN - NLM
STAT- MEDLINE
DCOM- 20141022
LR  - 20140128
IS  - 1095-8584 (Electronic)
IS  - 0022-2828 (Linking)
VI  - 67
DP  - 2014 Feb
TI  - Mechanical strain induces the production of spheroid mineralized microparticles 
      in the aortic valve through a RhoA/ROCK-dependent mechanism.
PG  - 49-59
LID - S0022-2828(13)00358-1 [pii]
LID - 10.1016/j.yjmcc.2013.12.009 [doi]
AB  - Calcific aortic valve disease (CAVD) is a chronic disorder characterized by an 
      abnormal mineralization of the leaflets, which is accelerated in bicuspid aortic 
      valve (BAV). It is suspected that mechanical strain may promote/enhance 
      mineralization of the aortic valve. However, the effect of mechanical strain and 
      the involved pathways during mineralization of the aortic valve remains largely 
      unknown. Valve interstitial cells (VICs) were isolated and studied under strain 
      conditions. Human bicuspid aortic valves were examined as a model relevant to 
      increase mechanical strain. Cyclic strain increased mineralization of VICs by 
      several-fold. Scanning electron microscope (SEM) and energy dispersive X-ray 
      (EDX) analyses revealed that mechanical strain promoted the formation of 
      mineralized spheroid microparticles, which coalesced into larger structure at the 
      surface of apoptotic VICs. Apoptosis and mineralization were closely associated 
      with expression of ENPP1. Inhibition of ENPP1 greatly reduced mineralization of 
      VIC cultures. Through several lines of evidence we showed that mechanical strain 
      promoted the export of ENPP1-containing vesicles to the plasma membrane through a 
      RhoA/ROCK pathway. Studies conducted in human BAV revealed the presence of 
      spheroid mineralized structures along with the expression of ENPP1 in areas of 
      high mechanical strain. Mechanical strain promotes the production and 
      accumulation of spheroid mineralized microparticles by VICs, which may represent 
      one important underlying mechanism involved in aortic valve mineralization. 
      RhoA/ROCK-mediated export of ENPP1 to the plasma membrane promotes strain-induced 
      mineralization of VICs.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Bouchareb, Rihab
AU  - Bouchareb R
AD  - Laboratoire d'Etudes Moleculaires des Valvulopathies (LEMV), Groupe de Recherche 
      en Valvulopathies (GRV), Quebec Heart and Lung Institute/Research Center, 
      Department of Surgery, Laval University, Quebec, Canada.
FAU - Boulanger, Marie-Chloe
AU  - Boulanger MC
AD  - Laboratoire d'Etudes Moleculaires des Valvulopathies (LEMV), Groupe de Recherche 
      en Valvulopathies (GRV), Quebec Heart and Lung Institute/Research Center, 
      Department of Surgery, Laval University, Quebec, Canada.
FAU - Fournier, Dominique
AU  - Fournier D
AD  - Laboratoire d'Etudes Moleculaires des Valvulopathies (LEMV), Groupe de Recherche 
      en Valvulopathies (GRV), Quebec Heart and Lung Institute/Research Center, 
      Department of Surgery, Laval University, Quebec, Canada.
FAU - Pibarot, Philippe
AU  - Pibarot P
AD  - Department of Medicine, Laval University, Quebec, Canada.
FAU - Messaddeq, Younes
AU  - Messaddeq Y
AD  - Department of Physics, Laval University, Quebec, Canada.
FAU - Mathieu, Patrick
AU  - Mathieu P
AD  - Laboratoire d'Etudes Moleculaires des Valvulopathies (LEMV), Groupe de Recherche 
      en Valvulopathies (GRV), Quebec Heart and Lung Institute/Research Center, 
      Department of Surgery, Laval University, Quebec, Canada. Electronic address: 
      patrick.mathieu@chg.ulaval.ca.
LA  - eng
GR  - MOP114893/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131222
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
RN  - 0 (Minerals)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
RN  - EC 3.1.4.- (Phosphoric Diester Hydrolases)
RN  - EC 3.1.4.1 (ectonucleotide pyrophosphatase phosphodiesterase 1)
RN  - EC 3.6.1.- (Pyrophosphatases)
RN  - EC 3.6.5.2 (rhoA GTP-Binding Protein)
SB  - IM
MH  - Aortic Valve/*pathology
MH  - Calcinosis/physiopathology
MH  - Cell Membrane/metabolism
MH  - Cell-Derived Microparticles/*metabolism
MH  - Cells, Cultured
MH  - Flow Cytometry
MH  - Gene Expression Regulation
MH  - Humans
MH  - Minerals/metabolism
MH  - Phosphoric Diester Hydrolases/genetics
MH  - Pyrophosphatases/genetics
MH  - *Stress, Mechanical
MH  - rho-Associated Kinases/*metabolism
MH  - rhoA GTP-Binding Protein/*metabolism
OTO - NOTNLM
OT  - Calcific aortic valve disease
OT  - ENPP1
OT  - Mineralized microparticles
OT  - RhoA
OT  - Strain
OT  - Valve interstitial cells
EDAT- 2013/12/26 06:00
MHDA- 2014/10/23 06:00
CRDT- 2013/12/26 06:00
PHST- 2013/08/23 00:00 [received]
PHST- 2013/11/14 00:00 [revised]
PHST- 2013/12/12 00:00 [accepted]
PHST- 2013/12/26 06:00 [entrez]
PHST- 2013/12/26 06:00 [pubmed]
PHST- 2014/10/23 06:00 [medline]
AID - S0022-2828(13)00358-1 [pii]
AID - 10.1016/j.yjmcc.2013.12.009 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 2014 Feb;67:49-59. doi: 10.1016/j.yjmcc.2013.12.009. Epub 
      2013 Dec 22.