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Bondareva, O. ; Hausner, M. ; Konert, M. ; Branzan, D. ; Noreikat, K.* ; Oßmann, S.* ; Sopromadze, L.* ; Geisler, A.* ; Heegaard, P.M.H.* ; Sheikh, B. ; Steiner, S.

Single-nucleus profiling of Ossabaw pig atherosclerosis model.

iScience 28:113464 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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; Smooth-muscle-cells; Artery Atherosclerosis; Calcification; Atlas; Mouse; Expression; Deficient; Protein; Thrombospondin-1; Association
Sprache englisch
Veröffentlichungsjahr 2025
HGF-Berichtsjahr 2025
ISSN (print) / ISBN 2589-0042
e-ISSN 2589-0042
Zeitschrift iScience
Quellenangaben Band: 28, Heft: 10, Seiten: , Artikelnummer: 113464 Supplement: ,
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)
POF Topic(s) 30201 - Metabolic Health
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-506502-001
G-555000-001
DOI 10.1016/j.isci.2025.113464
WOS ID 001593154500002
Scopus ID 105017610092
PubMed ID 41126895
Erfassungsdatum 2025-10-23
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