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A02 - Lipid-based control of the unfolded protein response in HFpEF

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Project summary

Obesity is a major contributing feature of HFpEF. Lipid overload occurring in HFpEF alters the homeostasis of the UPR (unfolded protein response) signaling pathway in cardiomyocytes. We have previously shown that UPR alterations are major driver of HFpEF pathogenesis. Here we set to comprehensively understand the role of the PERK (PKR-like endoplasmic reticulum kinase) arm of the UPR in HFpEF. To gain insights into the role of lipid biology in HFpEF, we will investigate the role of a lipid-based post-translational modification (PTM), S-palmitoylation, in PERK regulation in cardiomyocyte. Moving forward, we will dissect mechanisms of PERK-dependent modulation of cardiomyocyte response in HFpEF after exercise training - one of the few known beneficial interventions in this syndrome. Focusing on the fundamental mechanisms of lipid response in HFpEF- cardiomyocyte, we will contribute to the understanding of the metabolic alterations in this syndrome providing insights of scientific, and potentially clinical, relevance.


Graphical Abstract: Modulation of endoplasmic reticulum response by PERK Palmitoylation in HFpEF and exercised hearts. Ad: Adenovirus. siRNA: short interference RNA


Additional group members

Postdoc: Wang Rongling




Schiattarella GG, Alcaide P, Condorelli G, Gillette TG, Heymans S, Jones EAV, Kallikourdis M, Lichtman A, Marelli-Berg F, Shah S, Thorp EB, Hill JA. Immunometabolic Mechanisms of Heart Failure with Preserved Ejection Fraction. Nat Cardiovasc Res. 2022 Mar;1(3):211-222. doi: 10.1038/s44161-022-00032-w. Epub 2022 Mar 14. PMID: 35755006; PMCID: PMC9229992.

Bode D, Sotomayor-Flores C, Schiattarella GG. Up next: The dawn of systems biology in HFpEF research. J Mol Cell Cardiol. 2022 Jul;168:96-97. doi: 10.1016/j.yjmcc.2022.04.016. Epub 2022 Apr 27. PMID: 35489386.

Capone F, Sotomayor-Flores C, Bode D, Wang R, Rodolico D, Strocchi S, Schiattarella GG. Cardiac metabolism in HFpEF: from fuel to signalling. Cardiovasc Res. 2023 Feb 3;118(18):3556-3575. doi: 10.1093/cvr/cvac166. PMID: 36504368.