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SUMMARY:Haemodynamics and endothelial phenotype heterogeneity - Davies\, P
 F (Pennsylvania )
DTSTART:20090721T090000Z
DTEND:20090721T091500Z
UID:TALK19179@talks.cam.ac.uk
CONTACT:Mustapha Amrani
DESCRIPTION:Endothelial phenotype defines the multi-functional capabilitie
 s of the tissue (endothelial monolayer). Within coronary arteries and hear
 t valves\, as elsewhere in the arterial circulation\, the endothelial phen
 otype is spatially heterogeneous. Endothelial heterogeneity in general can
  be considered at different length scales from vascular beds to specialize
 d vascular structures such as heart valves to single cells and it arises f
 rom a combination of 'intrinsic' genetic programming and functional change
 s modified by epigenetic\, including important environmental\, influences.
  A prominent environmental influence is haemodynamics\, the usually comple
 x blood flow characteristics that arise from a combination of pulsatile fl
 ow\, the composition of blood elements\, and the geometry of the vessels. 
 Local changes of haemodynamics characteristics\, including the flow veloci
 ty\, direction\, frequency and oscillatory behaviour\, create two broad co
 nsequences in modifying endothelial structure and function. First the tran
 sport characteristics of (i) molecules derived from the cells themselves (
 e.g. short-lived regulatory molecules such as vasoregulators) and (ii) blo
 od molecules that are modified or degraded at the endothelial surface. The
  kinetics of these solutes is greatly influenced by changes in their trans
 port characteristics in the boundary layer near the cell surface. Second\,
  haemodynamic forces generated by flow\, particularly shear stress\, great
 ly influence endothelial biology (and pathophysiology)\; consequently the 
 steady state phenotype of endothelial cells is sensitive to the temporal-s
 patial distribution of the forces. Together\, the complex environment defi
 nes regions (and perhaps cellular foci) of endothelial phenotypes\, with c
 onsequences for the underlying artery wall. These mechanisms and their het
 erogeneous distribution are relevant to the incorporation of vascular biol
 ogy contributions to the cardiac physiome. I will discuss some of the flow
 -related mechanisms responsible for endothelial heterogeneity in coronary 
 arteries and valves gathered from genomics\, molecular biochemistry and fl
 uid dynamic experimentation\, and interpret their pathological implication
 s. Background References: Davies PF. Flow-mediated endothelial mechanotran
 sduction. Physiol. Rev. 1995\, 75:519-560. Davies PF. Polacek\, D.C.\, Shi
 \, C.\, Helmke\, B.P. The Convergence of Hemodynamics\, Genomics\, and End
 othelial Structure\, in Studies of the Focal Origin of Atherosclerosis. Bi
 orheology 2002\, 39: 299-306. Simmons\, C.A\, Manduchi\, E.\, Grant\, G.\,
  Davies\, P.F. 2005. Spatial heterogeneity of endothelial phenotypes corre
 lates with side-specific vulnerability to calcification in normal porcine 
 aortic valves. Circ. Research 96:792-799. Davies\, P.F. Hemodynamic Shear 
 Stress and the Endothelium in Cardiovascular Pathophysiology. Nature Clini
 cal Practice Cardiovasc. Medicine 2009\, 6:16-26. 
LOCATION:Seminar Room 1\, Newton Institute
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