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A05 - Role of sex hormones on microbiome, immunity, and coronary microvascular dysfunction and rarefication in experimental HFpEF

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Project summary

HFpEF is more often diagnosed in women, especially post menopause, but who on average face less effective care. We hypothesize sex differentially in HFpEF reflect 1) sex steroid impact directly or indirectly on gut microbiome, circulating metabolites, or immune system; in turn acting through 2) coronary microvascular dysfunction. Applying multi-omics technologies to animal models of HFpEF where endocrine sex can be manipulated, we will test this hypothesis and determine its specific microbial, immune and molecular drivers. Findings will be projected into the human setting by integrative and comparative analysis of host-microbiome data from this CRC and other sources.


Graphical Abstract: We will investigate the impact of sex steroids in HFpEF using preclinical (rodent models, this subproject) and clinical (patients, Z02 and elsewhere) data. We will especially assess whether cardiac microvascular dysfunction as HFpEF driver is mediated through microbiome and immune factors in turn responsive to shifting endocrinology such as seen during meno-/andropause. To this end we will integrate data from clinical phenotypes, microbiome sequencing and immune cytometry panels, modeling their interdependencies and evaluating their role in HFpEF


Additional group members

PhD Students: Nina Jovanovic, Sarah Kedziora

Technical Assistance: Jutta Meisel


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.

Fromentin S, Forslund SK, Chechi K, Aron-Wisnewsky J, Chakaroun R, Nielsen T, Tremaroli V, Ji B, Prifti E, Myridakis A, Chilloux J, Andrikopoulos P, Fan Y, Olanipekun MT, Alves R, Adiouch S, Bar N, Talmor-Barkan Y, Belda E, Caesar R, Coelho LP, Falony G, Fellahi S, Galan P, Galleron N, Helft G, Hoyles L, Isnard R, Le Chatelier E, Julienne H, Olsson L, Pedersen HK, Pons N, Quinquis B, Rouault C, Roume H, Salem JE, Schmidt TSB, Vieira-Silva S, Li P, Zimmermann-Kogadeeva M, Lewinter C, Søndertoft NB, Hansen TH, Gauguier D, Gøtze JP, Køber L, Kornowski R, Vestergaard H, Hansen T, Zucker JD, Hercberg S, Letunic I, Bäckhed F, Oppert JM, Nielsen J, Raes J, Bork P, Stumvoll M, Segal E, Clément K, Dumas ME, Ehrlich SD, Pedersen O. Microbiome and metabolome features of the cardiometabolic disease spectrum. Nat Med. 2022 Feb;28(2):303-314. doi: 10.1038/s41591-022-01688-4. Epub 2022 Feb 17. PMID: 35177860; PMCID: PMC8863577.