PMID- 20107896
OWN - NLM
STAT- MEDLINE
DCOM- 20110719
LR  - 20211020
IS  - 1573-6806 (Electronic)
IS  - 1567-8822 (Print)
IS  - 1567-8822 (Linking)
VI  - 10
IP  - 1
DP  - 2010 Mar
TI  - Hemodynamic environments from opposing sides of human aortic valve leaflets evoke 
      distinct endothelial phenotypes in vitro.
PG  - 5-11
LID - 10.1007/s10558-009-9089-9 [doi]
AB  - The regulation of valvular endothelial phenotypes by the hemodynamic environments 
      of the human aortic valve is poorly understood. The nodular lesions of calcific 
      aortic stenosis (CAS) develop predominantly beneath the aortic surface of the 
      valve leaflets in the valvular fibrosa layer. However, the mechanisms of this 
      regional localization remain poorly characterized. In this study, we combine 
      numerical simulation with in vitro experimentation to investigate the hypothesis 
      that the previously documented differences between valve endothelial phenotypes 
      are linked to distinct hemodynamic environments characteristic of these 
      individual anatomical locations. A finite-element model of the aortic valve was 
      created, describing the dynamic motion of the valve cusps and blood in the valve 
      throughout the cardiac cycle. A fluid mesh with high resolution on the fluid 
      boundary was used to allow accurate computation of the wall shear stresses. This 
      model was used to compute two distinct shear stress waveforms, one for the 
      ventricular surface and one for the aortic surface. These waveforms were then 
      applied experimentally to cultured human endothelial cells and the expression of 
      several pathophysiological relevant genes was assessed. Compared to endothelial 
      cells subjected to shear stress waveforms representative of the aortic face, the 
      endothelial cells subjected to the ventricular waveform showed significantly 
      increased expression of the "atheroprotective" transcription factor Kruppel-like 
      factor 2 (KLF2) and the matricellular protein Nephroblastoma overexpressed (NOV), 
      and suppressed expression of chemokine Monocyte-chemotactic protein-1 (MCP-1). 
      Our observations suggest that the difference in shear stress waveforms between 
      the two sides of the aortic valve leaflet may contribute to the documented 
      differential side-specific gene expression, and may be relevant for the 
      development and progression of CAS and the potential role of endothelial 
      mechanotransduction in this disease.
FAU - Weinberg, Eli J
AU  - Weinberg EJ
AD  - Department of Bioengineering, University of California, Berkeley, CA 94720, USA. 
      eli.alum@alum.mit.edu
FAU - Mack, Peter J
AU  - Mack PJ
FAU - Schoen, Frederick J
AU  - Schoen FJ
FAU - Garcia-Cardena, Guillermo
AU  - Garcia-Cardena G
FAU - Kaazempur Mofrad, Mohammad R
AU  - Kaazempur Mofrad MR
LA  - eng
GR  - T32 EB006348/EB/NIBIB NIH HHS/United States
GR  - R01-HL7066686/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Cardiovasc Eng
JT  - Cardiovascular engineering (Dordrecht, Netherlands)
JID - 101132083
SB  - IM
MH  - Aortic Valve/*physiology
MH  - Cells, Cultured
MH  - Computer Simulation
MH  - Endothelial Cells/*physiology
MH  - Endothelium, Vascular/*physiology
MH  - Gene Expression Regulation/*physiology
MH  - Humans
MH  - Mechanotransduction, Cellular/*physiology
MH  - *Models, Cardiovascular
MH  - Phenotype
MH  - Shear Strength/physiology
PMC - PMC2837826
EDAT- 2010/01/29 06:00
MHDA- 2011/07/20 06:00
PMCR- 2010/01/28
CRDT- 2010/01/29 06:00
PHST- 2010/01/29 06:00 [entrez]
PHST- 2010/01/29 06:00 [pubmed]
PHST- 2011/07/20 06:00 [medline]
PHST- 2010/01/28 00:00 [pmc-release]
AID - 9089 [pii]
AID - 10.1007/s10558-009-9089-9 [doi]
PST - ppublish
SO  - Cardiovasc Eng. 2010 Mar;10(1):5-11. doi: 10.1007/s10558-009-9089-9.