Objective
This project aims to better understanding of the molecular processes involved in carotid plaque morphology and seventy of vessel narrowing in the pathogenesis of ischaemic stroke associated with symptomatic and asymptomatic carotid stenosis. We propose to investigate the changes in gene activation, particularly those coding for angiogenic molecules and associated second messenger molecules in carotid plaques, serum and ischaemic brain following stroke. We will try to identify the link molecules between plaque pathology, serum cytokine expression and penumbra evolution in patients with symptomatic and asymptomatic carotid disease. Further we want to extend our observations in humans to in vitro and in vivo models. Beneficial or detrimental activation of each signal transduction pathway will be assessed on the base of cell survival and induction of apoptosis or necrosis in the carotid plaques and ischaemic penumbra.
The main objectives are the following:
1) Screening for changes in gene expression using Clontech Atlas multi-array technology. Important genes involved in signal transduction pathways will be identified and these will be studied in more detailes;
2) Immunohistochemistry, western blotting and protein activity studies for Fas, TNFRI, ras, raf, MAP-ERK family, PI3K, AKT, bad, Bclx-L;
3) Quantification of expression of the second messengers: PLC, PLA2, MAPK, and cytokines: VEGF, TGF, and PDGF families;
4) In the second year animal stroke model of focal cerebral ischaemia will be studied. The expression of the most important molecules will be compared with those found in humans;
5) Cell death mechanisms implicated in the plaque pathology will be studied. We will concentrate on the caspase-dependent and caspase-independent pathways. This will be compared to our initial studies in animal models.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesbasic medicinepathology
- medical and health sciencesbasic medicineneurologystroke
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Topic(s)
Data not availableCall for proposal
Data not availableFunding Scheme
RGI - Research grants (individual fellowships)Coordinator
08034 BARCELONA
Spain