A shared functional organisation underlies vascular disease remodelling

Cardiovascular disease encompasses a symphony of biological processes that work together in a synchronized manner. Gene-level signatures, which are unique to each study, share similarities across different experiments due to their common biological functions. While pathway-level analyses offer stable insights into these processes, they often treat each pathway separately.

Researchers proposed that clustering interconnected pathways into shared biological functions and assessing their relative influence could unveil a universal characteristic of vascular tissue, termed functional organisation. By evaluating the relative impact of six universal biological functions across separate transcriptomic datasets, they discovered a consistent functional organisation in vascular tissues, driven by the delicate balance of these functions.

This organisation is characterized by a dominant remodeling pattern that involves a nonlinear adjustment of structural, immune, signaling, and metabolic systems, as well as a second dimension that separates contractile/ECM organization from immune activity. This structural arrangement remains consistent across various reference cohorts and is resistant to changes in analytical methods.

When data from independent studies are placed within this established framework, biological and clinical findings align along a trajectory of remodeling. Furthermore, cellular populations derived from plaques, stromal cells, and immune cells also occupy distinct functional positions, correlating cellular diversity with tissue-level organization.

Notably, this organizational pattern is applicable to diverse vascular conditions, including atherosclerosis, peripheral vascular disease, and abdominal aortic aneurysm, and highlights a continuum of biological heterogeneity within traditional clinical classifications. Genetic, pharmacological, and dietary interventions consistently alter functional organization, indicating that the state of organization is not static but rather responsive to biological changes.

Overall, these findings establish functional organization as a stable tissue-level feature of vascular remodeling, offering a comprehensive framework to comprehend cardiovascular disease as a coordinated rebalancing of biological functions rather than isolated alterations of individual pathways.