From endovascular therapy to perivascular therapy: A new concept and perspective

Abstract

The cardiovascular system relies on an organ-spanning vascular network not only for transport but also for systemic homeostatic control. Surrounding the vessel wall is a complex perivascular microenvironment, including the vasa vasorum, autonomic and sensory nerves, perivascular adipose tissue, and lymphatics, which together constitute a neuro–immune–metabolic interface with regulatory reach far beyond hemodynamics. The close apposition and shared microanatomy of these components enable the coordinated control of vascular tone, remodeling, inflammation, tissue clearance, and organ function, creating a rich, multi-component therapeutic target space and access corridor for endovascular and extravascular interventions across cardiovascular and selected cardiometabolic disorders. However, therapies framed around a single nominal target often perturb multiple perivascular components, complicating mechanism attribution and contributing to heterogeneous responses. Emphasizing the perivascular microenvironment as an integrated domain makes whole-domain effects an important consideration, thereby forcing a clearer disentanglement of component-specific functions and treatment-linked adaptations. This whole-domain perspective underpins the concept of perivascular therapy and emphasizes the integration and co-development of device-based interventions and local drug-delivery strategies that target this microenvironment. Here, we synthesized the perivascular anatomy and physiology, surveyed established and emerging interventions, and outlined a roadmap integrating real-time imaging and mapping, targeted modulation, sensing-guided titration, and closed-loop control to enable precise, minimally invasive therapies targeting the perivascular microenvironment.