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HFpEF is hemodynamically characterized by an increase in left ventricular stiffness correlated with a rise in extracellular matrix. The project focuses on the integrin network and stiffness sensing and their contribution to modulate fibrosis as they regulate collagen formation and the cardiac invasion of inflammatory cells and fibrocytes. Hereby, this project will provide insights into how mechanosensitive pathways differ between HFpEF and HFrEF. Building on these findings, we will evaluate specific integrins as therapeutic targets to improve HFpEF treatment using small molecules.
Graphical Abstract: Via clinical samples and mouse models, regulation of the integrin network and its impact on cardiac remodeling will be analyzed involving molecular, cellular and physiological phenotyping.
Pesce M, Duda GN, Forte G, Girao H, Raya A, Roca-Cusachs P, Sluijter JPG, Tschöpe C, Van Linthout S. Cardiac fibroblasts and mechanosensation in heart development, health and disease. Nat Rev Cardiol. 2022 Nov 14. doi: 10.1038/s41569-022-00799-2. Epub ahead of print. PMID: 36376437.