Objective
Type 2 diabetes has become one of the major causes of cardiovascular risk factor-induced mortality in recent years. The severe endothelial dysfunction associated with diabetes leads to both macrovascular and microvascular disorders culminating in atherosclerosis and foot ulcers. The specific molecular mechanisms underlying this impaired neovascularization are incompletely understood. One of the main hypothesis is an altered function of progenitor cells derived from the bone marrow in diabetes, associated with a decreased number and a dysfunction of proangiogenic mononuclear/endothelial progenitor cells (EPC). We propose that the easily obtained EPC from patients reflect the more general endothelial dysfunction of the adult vasculature. Previous work from our groups has shown beneficial effects of shear stress and KLF2 (Krüppel-like factor 2) on endothelial function and normalization of MAPK networks as well as the specific role of phosphatases like PTP1B in diabetes. The aim of our project will focus on studying activation pathways involving deregulated phosphorylation cascades. Especially the infrequently studied phosphatases known to take part in diabetic pathology will be monitored in EPC isolated from diabetic and healthy subjects. Next, altered MAPKinase and phosphates relays will be studied in in vitro culture modulated by small molecule inhibitors or lentiviral genetic modulation. Specifically, the beneficial role of shear stress and its linked transcription factor KLF2 on EPC function will be assessed. Finally, we will evaluate the therapeutic capacity of identified inhibitors of specific kinases and phosphatases as well as KLF2 after a genetic or physiological (shear stress) overexpression to normalize EPC/endothelial function in a mouse model of revascularization after hindlimb ischemia. This study will thus contribute to the development of pharmaceutical targets and tools necessary for preventing clinical cardiovascular complications of diabetes.
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. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- social sciences sociology demography mortality
- medical and health sciences clinical medicine cardiology cardiovascular diseases arteriosclerosis
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine endocrinology diabetes
- medical and health sciences basic medicine pathology
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2009-IEF
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
1081 HV Amsterdam
Netherlands
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.