Research Details
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Project Leaders
Prof. Dr. Stefanie Dimmeler
Institute of Cardiovascular Regeneration
Goethe University Frankfurt
dimmeler@em.uni-frankfurt.de
Dr. Sebastian Cremer
Goethe University Frankfurt
cremer@med.uni-frankfurt.de
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Research Staff
Dr. David Rodriguez Morales (Postdoc)
Nina Murmann (PhD student)
s1012340@stud.uni-frankfurt.de
Leonie Stein (PhD Student)
Le.Stein@med.uni-frankfurt.de
In the previous funding period, we showed that global deletion of the lncRNA Ntras in mice induces cardiac inflammation even in steady state, associated with increased mortality of mice. Overshooting inflammation is an important contributor to heart failure after myocardial infarction. We will now characterize the mechanisms how Ntras deficiency induces this phenotype. Ntras is highly expressed in cardiac endothelial cells but also in leukocytes, which work synergistically in mounting an inflammatory response. We plan to determine whether NTRAS expression in endothelial cells, leukocytes, or both, restricts cardiac inflammation. We will use stateof- the art multicolor FACS analysis to characterize the effect of Ntras on the composition of immune cells after inflammatory challenges to the heart. Cell culture models, cardiac tissue mimetics, and genetic mouse studies, in which we will specifically delete Ntras in different cell lineages using floxed mice, will further help to define the direct involvement of endothelial and/or immune cells to the phenotype. We additionally will identify how Ntras and other lncRNAs control endothelial phenotypes after injury. We recently identified a CD45+ inflammatory endothelial cell population (IMEC) after myocardial infarction, which may be involved in recruitment and activation of immune cells. The IMEC-like phenotype can be induced by a local cytokine milieu namely IL1β, TGFβ2 and IFNγ in vitro. Our preliminary data show that Ntras levels and several other lncRNAs are reduced in IMECs, suggesting an involvement of lncRNAs in IMEC expansion. Therefore, we will dissect how Ntras and other lncRNAs in endothelial cells control IMEC emergence and cardiac inflammation.