Obiettivo
A critical event in the formation of mature atherosclerotic plaque is migration of smooth muscle cells (SMCs) from the media to the intima, where they produce extra-cellular matrix (ECM) proteins, forming a fibrous cap above the pro-inflammatory and lipid core. SMC are highly plastic, and can alter their state of differentiation in response to environmental cues. Intimal SMC display pro-inflammatory properties, in that expression of the adhesion molecule P-selectin and cytokines are up-regulated and NFkB is activated. It is not explicitly known what triggers the pro-inflammatory phenotype of SMCs. We propose to utilize human carotid atheroma-derived SMC from endarterectomy specimens to identify the molecular basis of the pro-inflammatory phenotype of SMC in atherosclerosis via transcriptome analysis. Determining the specific gene expression pattern of SMCs in atherosclerotic plaques as well as in healthy tissue helps in gaining a better understanding of the plaque formation process. Since the oral cavity is well vascularized, we also hypothesize that infection in this site provides a direct route to the bloodstream and might contribute to plaque inflammation and changes in SMC responses. We will study whether biological samples from human periapical abscesses can induce inflammatory gene expression in SMC by using aspirates of bacteria from lesions of periodontal infection (containing bacteria such as Actinobacillus actinomycetemcomitans or Porhyromonas gingivalis) as well as contents of periapical abscesses from dental patients. The study of such pro-inflammatory events might provide insights into the development and/or destabilization of atherosclerotic plaque. The strong merit of the proposed study is the use of relevant human tissues which increases the translational value of the research and the possibility to understand human disease.
Campo scientifico (EuroSciVoc)
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP. Cfr.: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifica i progetti con EuroSciVoc, una tassonomia multilingue dei campi scientifici, attraverso un processo semi-automatico basato su tecniche NLP. Cfr.: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- scienze naturaliscienze biologichemicrobiologiabatteriologia
- scienze mediche e della salutemedicina clinicacardiologiamalattie cardiovascolariarteriosclerosi
- scienze naturaliscienze biologichebiochimicabiomolecoleproteine
- scienze naturaliscienze biologichebiochimicabiomolecolelipidi
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Argomento(i)
Invito a presentare proposte
FP7-PEOPLE-2009-IEF
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Meccanismo di finanziamento
MC-IEF - Intra-European Fellowships (IEF)Coordinatore
OX1 2JD Oxford
Regno Unito