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A06 - Immune regulation of vascular rarefaction and diastolic myocardial remodeling

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Project summary

We aim to exploit two model systems, zebrafish and rat, to uncover cellular and molecular mechanisms of immune-vascular-cardiac interaction in HFpEF pathogenesis. Our goals are to understand how immune signaling participates in vascular and cardiac remodeling and to tackle the role of the gut microenvironment on the pathogenic pathway through its influence on immune homeostasis. Furthermore, involvement of immune signaling in cardiac metabolic derangement will be examined. Finally, we will identify therapeutic candidates, from commensal microbial metabolites, capable of regulating the multi-systemic crosstalk and test their efficacy in vascular and cardiac protection.

 

Graphical Abstract: We will employ two experimental  models, zebrafish and rat, to capture cardiac and extracardiac pathophysiology of HFpEF. By different multi-omic approaches and cross comparison of the data from both models,  we aim to determine molecular hallmarks of immune and metabolic alteration and to identify microbial metabolites capable of alleviating vascular rarefaction and cardiac diastolic dysfunction. Cellular interaction and molecular  crosstalk between immune and metabolic pathways will also be elucidated.

Team

Additional group members

PhD students: Bhakti Irene Zakarauskas-Seth

Postdoc: Florian Herse

 

 

 


Publications

Ercu M, Mücke MB, Pallien T, Markó L, Sholokh A, Schächterle C, Aydin A, Kidd A, Walter S, Esmati Y, McMurray BJ, Lato DF, Yumi Sunaga-Franze D, Dierks PH, Flores BIM, Walker-Gray R, Gong M, Merticariu C, Zühlke K, Russwurm M, Liu T, Batolomaeus TUP, Pautz S, Schelenz S, Taube M, Napieczynska H, Heuser A, Eichhorst J, Lehmann M, Miller DC, Diecke S, Qadri F, Popova E, Langanki R, Movsesian MA, Herberg FW, Forslund SK, Müller DN, Borodina T, Maass PG, Bähring S, Hübner N, Bader M, Klussmann E. Mutant Phosphodiesterase 3A Protects From Hypertension-Induced Cardiac Damage. Circulation. 2022 Dec 6;146(23):1758-1778. doi: 10.1161/CIRCULATIONAHA.122.060210. Epub 2022 Oct 19. PMID: 36259389.

Holle J, Bartolomaeus H, Löber U, Behrens F, Bartolomaeus TUP, Anandakumar H, Wimmer MI, Vu DL, Kuhring M, Brüning U, Maifeld A, Geisberger S, Kempa S, Schumacher F, Kleuser B, Bufler P, Querfeld U, Kitschke S, Engler D, Kuhrt LD, Drechsel O, Eckardt KU, Forslund SK, Thürmer A, McParland V, Kirwan JA, Wilck N, Müller D. Inflammation in Children with CKD Linked to Gut Dysbiosis and Metabolite Imbalance. J Am Soc Nephrol. 2022 Dec;33(12):2259-2275. doi: 10.1681/ASN.2022030378. Epub 2022 Aug 19. PMID: 35985814; PMCID: PMC9731629.

Apaydin DC, Zakarauskas-Seth BI, Carnevale L, Apaydin O, Perrotta M, Carnevale R, Kotini MP, Kotlar-Goldaper I, Belting HG, Carnevale D, Filosa A, Sawamiphak S. Interferon-γ drives macrophage reprogramming, cerebrovascular remodeling, and cognitive dysfunction in a zebrafish and a mouse model of ion imbalance and pressure overload. Cardiovasc Res. 2022 Dec 20:cvac188. doi: 10.1093/cvr/cvac188. Epub ahead of print. PMID: 36536484.