Objective
Survivors of acute myocardial infarction (MI) are at a particularly high risk for accelerated atherosclerosis and recurrent atherothromobosis. Nevertheless, mechanistic preclinical studies in atherosclerosis research world-wide are typically conducted in unchallenged (without MI) atherosclerosis-prone mice and thus do not address the specific pathophysiology of post-MI atherosclerotic cardiovascular disease. We conducted a single-cell RNA sequencing coupled to B cell receptor (BCR) sequencing analysis of sorted CD45+ splenocytes from atherosclerosis-prone mice that were fed an atherogenic diet for eight weeks in total and were subjected four weeks after the initiation of the atherogenic diet feeding either to sham microsurgery or to permanent ligation of the left anterior descending coronary artery to induce MI. We found that splenic mature B lymphocytes from atherosclerotic mice that suffered an MI display altered glucocorticoid-induced responses and a more diversified BCR repertoire, which contains twelve unique clonotypes (named B-MIracle clones) that are not present in atherosclerotic mice without MI.
Here, I aim a) to investigate the effect of glucocorticoid-induced signaling in B cells in post-MI atherosclerosis in vivo by employing mouse models that allow the inducible genetic manipulation of different components of the glucocorticoid-induced signaling axis, b) by utilizing the full heavy and light chain nucleotide sequences from our single cell BCR-seq data, to clone and produce the respective antibodies of the B-MIracle clones and examine their effect in accelerated atherosclerosis after MI in vivo, and c) to address the relevance of these findings in atherosclerosis progression in patients with a recent MI, by analyzing sorted peripheral B cell subsets and serum samples. These studies may lead to the identification of precise therapeutic targets for secondary prevention of cardiovascular 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.
- medical and health sciences basic medicine physiology pathophysiology
- medical and health sciences clinical medicine cardiology cardiovascular diseases arteriosclerosis
- medical and health sciences health sciences nutrition
- natural sciences biological sciences genetics RNA
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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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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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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.
HORIZON-ERC - HORIZON ERC Grants
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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) ERC-2021-STG
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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.
1090 WIEN
Austria
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.