Project description
Blood vessel fat: a new target for diabetes treatment
Type 2 diabetes is one of the strongest risk factors for cardiovascular disease, doubling the likelihood of developing coronary artery disease through mechanisms that remain incompletely understood. Fat tissue surrounding blood vessels has recently emerged as an active regulator of vascular health, releasing signalling molecules that affect blood vessel function. With the support of the Marie Skłodowska-Curie Actions programme, the IMAPERFAT project aims to investigate cell-specific molecular changes in the perivascular fat tissue in type 2 diabetes. Researchers will employ human biopsies from patients undergoing bypass surgery to map secreted factors and determine their effects on vascular function. The goal is to identify novel biomarkers and therapeutic targets for diabetic cardiovascular disease.
Objective
Cardiovascular disease (CVD), such as coronary artery disease (CAD), is currently the largest global killer. Despite current therapeutic measures, patients with type 2 diabetes (T2DM) present a two-fold increased risk of developing CAD compared to people without T2DM. This highlights the unmet medical need for more powerful preventive/therapeutic measures for T2DM-linked CAD. One of the emerging anti-T2DM-linked CAD targets is the perivascular adipose tissue (PVAT), which releases various factors to mediate local vascular endothelial function. As endothelial dysfunction, reflected by impaired vasorelaxation, in T2DM is closely linked to the development of CVD, targeting PVAT-vascular endothelium crosstalk may open a new therapeutic window.
In this study (IMAPERFAT), the aim is to determine cell-type-specific molecular changes in PVAT in T2DM, and functionally test their therapeutic potential to prevent/treat T2DM-linked endothelial dysfunction and CVD. Using our newly set up biobank of human internal mammary artery (IMA) and its adjacent PVAT biopsies isolated from patients undergoing coronary artery bypass grafting surgery, with CAD with and without T2DM, three research objectives are set out: (1) To characterise cell-type-specific secretory signatures of IMA-PVAT in T2DM (by single-nucleus RNA-sequencing and integrating transcriptomics with paired proteomics of PVAT-conditioned media) (2) To determine the effect of PVAT-released factors on vascular endothelial function in T2DM; (3) set up a translational T2DM-PVAT spheroid model to target adverse PVAT remodelling.
IMAPERFAT will yield a novel transcriptomic dataset of human IMA-PVAT on a single-cell level resolution and may lead to the discovery of biomarker/therapeutic targets for T2DM-linked PVAT and endothelial dysfunction. It is also a fantastic training opportunity for me to develop my interdisciplinary academic research expertise with clinicians and industry partners in the European Union.
Fields of science (EuroSciVoc)
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- natural sciences biological sciences biochemistry biomolecules proteins proteomics
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HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA)
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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-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships
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(opens in new window) HORIZON-MSCA-2025-PF
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171 77 STOCKHOLM
Sweden
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