MACOBESITY

The obesity-induced macrophage: a new player in atherosclerosis development

 Coordinatore UNIVERSITEIT MAASTRICHT 

 Organization address address: Minderbroedersberg 4-6
city: MAASTRICHT
postcode: 6200 MD

contact info
Titolo: Mr.
Nome: Robert
Cognome: Van Der Zander
Email: send email
Telefono: +31 433881645

 Nazionalità Coordinatore Netherlands [NL]
 Totale costo 100˙000 €
 EC contributo 100˙000 €
 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-2012-CIG
 Funding Scheme MC-CIG
 Anno di inizio 2012
 Periodo (anno-mese-giorno) 2012-09-01   -   2016-08-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    UNIVERSITEIT MAASTRICHT

 Organization address address: Minderbroedersberg 4-6
city: MAASTRICHT
postcode: 6200 MD

contact info
Titolo: Mr.
Nome: Robert
Cognome: Van Der Zander
Email: send email
Telefono: +31 433881645

NL (MAASTRICHT) coordinator 100˙000.00

Mappa


 Word cloud

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

atms    mice    cd    fatty    immune    tissue    obesity    vivo    cells    adipose    obese    ldlr    link    macrophages    bone    free    recruitment    functional    positive    marrow    acids    atherogenesis    phenotype    differentiation    atherosclerosis    ffas   

 Obiettivo del progetto (Objective)

'Obesity is an independent risk factor for atherosclerosis but the exact mechanistic link between these conditions is unknown. Parallel to atherogenesis, obesity induces the recruitment of pro-inflammatory macrophages from bone marrow to adipose tissue (AT). We hypothesize that obesity-induced macrophages, through interactions with adipose tissue-derived free fatty acids, are important players in atherosclerosis development and thereby represent the key link between these conditions. First, we will investigate the effects of obese AT on the phenotype and function of adipose tissue macrophages (ATMs) and the consequences for atherogenesis. Since it is known that obesity leads to recruitment of CD11c-positive, dendritic cell-like ATMs, the effects of local AT-derived free fatty acids (FFAs) on ATM phenotype and their antigen-presenting capacity will be assessed in vitro and in vivo using mouse models. Additionally, we will isolate CD11c-positive and CD11c-negative (resident) ATMs from obese AT and compare them by genome-wide expression analysis and functional studies. Moreover, the effects of ATMs on adaptive immune responses and atherosclerosis will be assessed by transplantation of obese AT to atherosclerosis-prone low-density lipoprotein receptor deficient (ldlr-/-) mice. Second, we will investigate the effects of FFAs on the differentiation of macrophages from bone marrow cells and the consequences for atherosclerosis development. Hereto, we will determine how FFAs affect differentiation of bone marrow cells into macrophages by performing functional characterization. The obtained results will be evaluated in vivo by adoptive transfer of bone marrow-derived macrophages, treated ex vivo with FFAs during their differentiation, to ldlr-/- mice. Atherosclerosis development and alterations in the immune response will be measured in detail. Finally, we will validate the results in human patient material identifying novel diagnostic markers and therapeutic targets.'

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