A shared functional organisation underlies vascular disease remodelling
- 1Royal Veterinary College
Abstract
Cardiovascular disease involves coordinated remodelling across multiple biological processes. Gene-level signatures vary substantially between studies because different combinations of genes can support similar biological processes. Pathway-level analyses can provide more stable representations of these processes but typically consider pathways independently. We hypothesised that grouping related pathways into conserved biological functions and quantifying their relative weighting would reveal a higher-order, transferable property of vascular tissue that we term functional organisation. We quantified the relative weighting of six conserved biological functions across independent transcriptomic datasets spanning human vascular disease, experimental models and therapeutic interventions. Vascular tissues exhibited a reproducible functional organisation defined by the balance of these functions. A dominant remodelling trajectory captured coordinated, nonlinear rebalancing of structural, immune, signalling and metabolic programmes, while a second dimension distinguished contractile/ECM organisation from immune activity. This organisation was preserved across independently reconstructed reference cohorts and remained robust to analytical sensitivity testing. When independent datasets were projected into this fixed framework, biological and clinical phenotypes occupied coherent positions along the remodelling landscape. Plaque-derived vascular, stromal and immune cell populations also occupied ordered functional positions, linking cellular heterogeneity to tissue-level organisation. The same organisational structure generalised across atherosclerosis, peripheral vascular disease and abdominal aortic aneurysm and revealed continuous biological heterogeneity within conventional clinical classifications. Genetic, pharmacological and dietary perturbations reproducibly shifted functional organisation, demonstrating that organisational state is dynamic and biologically responsive. Together, these findings identify functional organisation as a reproducible tissue-level property of vascular remodelling and provide a framework for understanding cardiovascular disease as coordinated rebalancing of biological functions rather than alteration of individual pathways in isolation.
Related
- A post-embryonic specific and ecologically selective network underlies metamorphic remodelling in teleosts
- Functional reorganization of large-scale brain systems underlies emotion regulation maturation
- Anatomical and functional organisation of the cholinergic nervous system in the tunicate Botryllus schlosseri
- Development of Neonatal Functional Brain Network Organisation and Its Association with Childhood Neurodevelopmental Outcomes
- Longitudinal fMRI reveals altered developmental trajectories of functional network organisation associated with adolescent cannabis use
BibTeX
@misc{bradford2026shared,
title = {{A shared functional organisation underlies vascular disease remodelling}},
author = {A. Bradford and S. Bidula and L. Fabian and D. Warren},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.03.749124},
url = {https://www.biorxiv.org/content/10.64898/2026.09.03.749124v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A shared functional organisation underlies vascular disease remodelling
AU - A. Bradford
AU - S. Bidula
AU - L. Fabian
AU - D. Warren
PY - 2026
DA - 2026/09/03
PB - bioRxiv
DO - 10.64898/2026.09.03.749124
UR - https://www.biorxiv.org/content/10.64898/2026.09.03.749124v1
AB - Cardiovascular disease involves coordinated remodelling across multiple biological processes. Gene-level signatures vary substantially between studies because different combinations of genes can support similar biological processes. Pathway-level analyses can provide more stable representations of these processes but typically consider pathways independently. We hypothesised that grouping related pathways into conserved biological functions and quantifying their relative weighting would reveal a higher-order, transferable property of vascular tissue that we term functional organisation. We quantified the relative weighting of six conserved biological functions across independent transcriptomic datasets spanning human vascular disease, experimental models and therapeutic interventions. Vascular tissues exhibited a reproducible functional organisation defined by the balance of these functions. A dominant remodelling trajectory captured coordinated, nonlinear rebalancing of structural, immune, signalling and metabolic programmes, while a second dimension distinguished contractile/ECM organisation from immune activity. This organisation was preserved across independently reconstructed reference cohorts and remained robust to analytical sensitivity testing. When independent datasets were projected into this fixed framework, biological and clinical phenotypes occupied coherent positions along the remodelling landscape. Plaque-derived vascular, stromal and immune cell populations also occupied ordered functional positions, linking cellular heterogeneity to tissue-level organisation. The same organisational structure generalised across atherosclerosis, peripheral vascular disease and abdominal aortic aneurysm and revealed continuous biological heterogeneity within conventional clinical classifications. Genetic, pharmacological and dietary perturbations reproducibly shifted functional organisation, demonstrating that organisational state is dynamic and biologically responsive. Together, these findings identify functional organisation as a reproducible tissue-level property of vascular remodelling and provide a framework for understanding cardiovascular disease as coordinated rebalancing of biological functions rather than alteration of individual pathways in isolation.
ER -