Presenter Frank van Steenbeek
Authors Talitha C F Spanjersberg1,2,3*, Alma H Hulsman1*, Guy C M Grinwis4, Babette Janssen2,3, C Nina van der Wilt3,4, Rogier J A Veltrop2,3,5,6, Christian Snijders Blok2,3, Claudia Rozendom1, Paul Besseling2,7, Jolanda van der Velden8, Pim van der Harst3, Magdalena Harakalova2,3,5,6#, Frank G van Steenbeek1,2,3#
Affiliations 1Department Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands. 2Regenerative Medicine Center Utrecht (RMCU), UMC Utrecht, University of Utrecht, The Netherlands 3Department of Cardiology, Division Heart & Lungs, UMC Utrecht, University of Utrecht, Utrecht, The Netherlands 4Department Biomolecular Health Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands 5Department of Biochemistry, CARIM, Maastricht University, Maastricht, The Netherlands 6Netherlands Heart Institute, Holland Heart House, Utrecht, The Netherlands 7Department of Nephrology and Hypertension, UMC Utrecht, University of Utrecht, 3584 CX Utrecht, The Netherlands 8Department of Physiology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, Amsterdam, The Netherlands * and # equal contribution
Presentation Type Talk
Abstract
Hypertrophic cardiomyopathy (HCM) is a naturally occurring disease in domestic cats displaying genetic, clinical, and pathological similarities to humans, highlighting their value as a biologically pertinent but as of yet underutilized model. While feline HCM affects 14.7% of cats compared to 0.2% of humans, systematic studies linking cardiac remodeling with clinical outcomes are lacking. We aimed to comprehensively characterize feline HCM in a cross-sectional cohort using advanced histological and transcriptomic approaches to bridge this gap.
We analyzed midventricular cardiac sections from 37 cats with arterial thromboembolism (ATE), congestive heart failure (CHF) without ATE, or no documented heart disease. Semi-automated machine and deep learning image analysis quantified fibrosis, adipocyte infiltration, vascular morphology, and nuclear shape. Additionally, we performed Nanopore long-read direct RNA sequencing to link histological features with transcriptomic profiles. Cats with ATE showed increased myocardial fibrosis, whereas CHF cats did not differ significantly from controls, suggesting distinct remodeling pathways. Nuclear hypertrophy was prominent in CHF but not in cats with ATE. Fibrosis correlated with suppressed mitochondrial and contractile gene expression. Adipocyte infiltration mirrored patterns seen in human hearts and inversely correlated with immune-related gene expression, indicating potential anti-inflammatory roles.
This study establishes a high-resolution, multimodal framework for investigating hypertrophic cardiomyopathy in the domestic cat. By combining scalable histological quantification with transcriptomic and targeted gene expression analysis, we demonstrate the translational relevance of this model and its potential to translate basic research into clinical applications.