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Single-nucleus profiling of Ossabaw pig atherosclerosis model.
iScience 28:113464 (2025)
Verlagsversion
Forschungsdaten
DOI
PMC
Atherosclerosis is a major cause of cardiovascular disease, and accurate preclinical models are essential for developing effective therapies. The Ossabaw pig model has high potential due to its physiological similarity to humans, but its molecular characterization remains limited. To address this, we performed single-nucleus RNA sequencing of over 36,000 nuclei from aortas of Ossabaw pigs fed chow or atherogenic diets. Our analysis revealed activation of brain-derived neurotrophic factor (BDNF), transforming growth factor β (TGF-β), SPP1, and interleukin-2 (IL-2) signaling pathways in atherosclerosis, along with smooth muscle cell transitions to synthetic and pro-osteogenic states, endothelial-to-mesenchymal transition, and TREM2+ immune cell phenotypes. Advanced fibrotic, immune cell-infiltrated plaques with calcification sites paired with molecular changes closely resembled those seen in human atherosclerosis. Together, our findings establish the Ossabaw pig as a valuable translational model and provide high-resolution data to support its use in preclinical cardiovascular research.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Cardiovascular Medicine ; Model Organism ; Porcine ; Transcriptomics
ISSN (print) / ISBN
2589-0042
e-ISSN
2589-0042
Zeitschrift
iScience
Quellenangaben
Band: 28,
Heft: 10,
Artikelnummer: 113464
Verlag
Elsevier
Verlagsort
Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis
Begutachtungsstatus
Peer reviewed
Institut(e)
Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)