Project description
Dissecting the molecular mechanism of thrombosis in diabetes
Type 2 diabetes (T2D) patients have a higher risk of developing cardiovascular disease, owing to the hyperactivity of platelets that lead to thrombosis. Researchers of the EU-funded POSTA project are working on NADPH oxidases (NOXs), enzymes that produce reactive oxygen and are implicated in various physiological processes. Recent evidence indicates that NOXs also activate platelets. Therefore, POSTA proposes to investigate the molecular mechanism by which NOX enzymes cause vascular complication in T2D. Apart from fundamental knowledge on platelet activation, project results may lead to novel interventions against T2D.
Objective
Platelets are circulating blood cells that help to arrest of bleeding (i.e. haemostasis) and promote the repair of blood vessels following injury. In type 2 diabetes mellitus (T2DM), platelets are hyperactive and their uncontrolled activation leads to the unwanted occlusion of blood vessels (i.e. thrombosis). Thrombosis is the main cause of mortality for T2DM patients, who display significantly higher risk of cardiovascular disease than the rest of the population. Currently, 70% of T2DM patients succumb to cardiovascular diseases.
I have been working on pro-oxidant enzymes called NADPH oxidases (NOXs), which are responsible for oxidative stress and activation of platelets. I have shown that the enzymatic activity of NOXs generates oxidant molecules (i.e. free radicals), which in turn are responsible for platelet activation. In preparation to this application, I have generated data showing that platelets from T2DM patients contain higher levels of the NOX1 isoform. This enzyme is responsible for oxidative stress and hyperactivity of platelets from T2DM platelets compared to healthy controls.
In this project, I aim to understand the molecular mechanisms underlying platelet regulation by NOXs and the contribution of NOX1 to platelet hyperactivity in T2DM. I will use human blood from T2DM patients and murine models of T2DM. In addition to clarifying the role of NOX1 in the vascular complications of T2DM, I will test whether NOX1 inhibitors synthesised in my laboratory can protect the health of the vascular system in this disease.
Taken together, this project will markedly advance our understanding of how platelets are regulated and will generate novel information on the link between cardiovascular risk and T2DM, which may result in a substantial improvement of the clinical management of this disease.
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 angiology vascular diseases
- medical and health sciences clinical medicine endocrinology diabetes
- medical and health sciences clinical medicine cardiology cardiovascular diseases
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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.
(opens in new window) H2020-MSCA-IF-2020
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
20251 Hamburg
Germany
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.