ARTERIOGENESIS IN TRANSLATION (ARTIST) | 2025

• Christiana RUHRBERG, University College London (UK)
• Brian ANNEX, Medical College of Georgia (USA)

Peripheral arterial disease (PAD), caused by poor blood flow to the legs, is a major cause of illness and death across the globe. It occurs when arteries become too narrow to carry sufficient blood, are blocked or regress entirely. Clinical trials aiming to improve blood flow to muscles by regenerating or remodeling blood vessels have repeatedly failed, highlighting our limited knowledge of the mechanisms that could be harnessed for successful therapy. Here, we propose ARTIST as an international network of clinicians, vascular biologists, physicists, and biomedical engineers to first build a conceptual framework of the regulatory networks that govern artery formation, and then use this information to develop new treatments for PAD. ARTIST builds on paradigm-shifting pilot data and innovative methods to unravel how complex interactions between vascular endothelial growth factor (VEGF) and fluid shear stress (FSS) from flowing blood promote blood vessel growth and enlargement. Our study will investigate how vascular cells sense blood flow and develop methods to enhance activation of these pathways for therapeutic innovation. ARTIST leverages: i.) the novel cSTAR computational method, which integrates AI and machine learning for an unprecedented understanding of regulatory signaling networks; ii.) blood vessel-on-a-chip models and mechanopharmacology approaches; iii.) animal models that are relevant to human disease to test novel methods for treating PAD; iv.) a unique biobank of diverse specimens from patients with PAD to establish clinical relevance of our findings. Throughout the project, the ARTIST network will consider the effect of diabetes, inflammation, aging, and male versus female sex. By combining a world-class, innovative and interdisciplinary environment with dedicated resources, ARTIST will also train the next generation of young scientists. In this manner, the ARTIST network will catalyze the development of new treatments for PAD and other diseases caused by poor blood flow to tissues.