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Single-nucleus profiling of Ossabaw pig atherosclerosis model
Olga Bondareva1,2, Marlene Hausner1,2, Manuela Konert1,2
1Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Center Munich at the University of Leipzig and University Hospital Leipzig, Leipzig, Germany.
Iscience
|October 23, 2025
Summary
The Ossabaw pig model shows molecular changes similar to human atherosclerosis, including specific signaling pathways and cell transitions. This validates its use for preclinical cardiovascular disease research.
Area of Science:
- Cardiovascular Research
- Translational Medicine
- Atherosclerosis Modeling
Background:
- Atherosclerosis is a leading cause of cardiovascular disease, necessitating robust preclinical models.
- The Ossabaw pig shares physiological similarities with humans, but lacks comprehensive molecular characterization for atherosclerosis studies.
Purpose of the Study:
- To molecularly characterize the Ossabaw pig aorta under different dietary conditions.
- To evaluate the suitability of the Ossabaw pig as a translational model for human atherosclerosis.
Main Methods:
- Single-nucleus RNA sequencing (snRNA-seq) was performed on over 36,000 nuclei from Ossabaw pig aortas.
- Pigs were fed either a standard chow or an atherogenic diet to induce atherosclerotic changes.
Main Results:
- Identified activation of brain-derived neurotrophic factor (BDNF), transforming growth factor β (TGF-β), SPP1, and interleukin-2 (IL-2) signaling pathways in atherosclerosis.
- Observed smooth muscle cell transitions to synthetic and pro-osteogenic states, endothelial-to-mesenchymal transition, and TREM2+ immune cell phenotypes.
- Atherosclerotic plaques exhibited advanced fibrosis, immune cell infiltration, and calcification, mirroring human disease characteristics.
Conclusions:
- The Ossabaw pig model accurately recapitulates key molecular and pathological features of human atherosclerosis.
- This study provides high-resolution molecular data, establishing the Ossabaw pig as a valuable translational model for preclinical cardiovascular research.
