S1PWSSECPERMEABILITY

Correlation Between Numerical Estimation of In Vivo Local Sphingosine-1-Phosphate Concentration and Endothelial Permeability

 Coordinatore IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE 

 Organization address address: SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
city: LONDON
postcode: SW7 2AZ

contact info
Titolo: Mr.
Nome: Shaun
Cognome: Power
Email: send email
Telefono: +44 20 7594 8773
Fax: +44 20 7594 8609

 Nazionalità Coordinatore United Kingdom [UK]
 Totale costo 210˙092 €
 EC contributo 210˙092 €
 Programma FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call FP7-PEOPLE-2010-IIF
 Funding Scheme MC-IIF
 Anno di inizio 2011
 Periodo (anno-mese-giorno) 2011-11-01   -   2013-10-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE

 Organization address address: SOUTH KENSINGTON CAMPUS EXHIBITION ROAD
city: LONDON
postcode: SW7 2AZ

contact info
Titolo: Mr.
Nome: Shaun
Cognome: Power
Email: send email
Telefono: +44 20 7594 8773
Fax: +44 20 7594 8609

UK (LONDON) coordinator 210˙092.80

Mappa


 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

permeability    flow    spatial    mouse    wall    platelets    shear    atherosclerosis    endothelial    wss    shown    recently    blood    concentration    vitro          lipoprotein    local    hdl    heterogeneity    density    aorta   

 Obiettivo del progetto (Objective)

'Increased endothelial permeability allows accumulation of low-density lipoprotein (LDL) in the artery wall and may lead to atherosclerosis. The spatial heterogeneity of atherosclerosis has been thought to implicate flow mediated effects in the development of the disease. Indeed both in vitro and in vivo studies have shown a correlation between low or oscillating wall shear stress (WSS) and increases in atherogenic factors including increased endothelial permeability. However, the mouse, which has been used extensively as a model of atherosclerosis, has been shown to have high WSS in the aorta with little spatial variation. And yet, the mouse exhibits strong spatial heterogeneity in atherosclerotic lesion development. Therefore factors other than WSS must play a significant role. There are a number of molecules with known effects on endothelial permeability and recently the sphingolipid, sphingosine-1-phosphate (S1P), has been shown to reduce permeability of endothelial cells in vitro. Platelets have long been known to have a protective effect on the endothelium and recently it was shown that S1P is the major barrier protector in platelets. Therefore it is hypothesized that: endothelial permeability correlates inversely with the combined local WSS and S1P concentration. This hypothesis will be tested by comparing measurements of endothelial permeability in the mouse aorta with estimates of the local S1P concentration and WSS as calculated using numerical blood flow modelling. The state-of-the-art imaging technique of ultrasound-particle image velocimetry will be used to measure the velocity in the aorta which will be the basis of the simulation. The latest methods will be used for modelling blood as a multiphase fluid, and convection-diffusion-reaction equations will be developed to describe the shear activation of platelets and subsequent S1P release, S1P combining with high density lipoprotein (HDL), and then the distribution of HDL-S1P in the near-wall region.'

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