Ventricular cardiomyocyte signal compartmentation and functional reserve in HFpEF (A01)

HFpEF is a multifactorial systemic disease, characterized by cardiac structural remodeling and an inadequate augmentation of cardiac contractile function upon physiological stress. CM contractile function at baseline and its functional contractile reserve are regulated by compartmentalization of the main second messengers, cAMP and Ca2+, in highly controlled intracellular functional microdomains. We hypothesize that HFpEF is associated with molecular-level alterations in intracellular cAMP- and Ca2+ signaling microdomains, which limit the functional reserve of the CM. We aim at establishing alterations of β-adrenoreceptor -subtype /cAMP- and Ca2+ dynamics and the impact on the functional reserve with physiological inotropic stimuli (adrenergic, frequency, stretch) in metabolic vs non-metabolic HFpEF. In addition, we investigate the effects of acute metabolic stress on the cardiomyocyte functional reserve in HFpEF and explore underlying mechanisms.

DFG Programme Collaborative Research Centres

Subproject of SFB 1470:  Multilevel mechanistic characterisation of Heart Failure with Preserved Ejection Fraction - Towards a novel classification of HFpEF for targeted therapies

Applicant Institution shared FU Berlin and HU Berlin through:
Charité - Universitätsmedizin Berlin

Project Heads Dr. Paolo Annibale, until 12/2023; Professor Frank Heinzel, Ph.D., until 2/2023; Privatdozent Felix Hohendanner, Ph.D., since 3/2023