Proteases and Protease Inhibitors in Vascular Dysfunction and Therapy

The field of vascular biology is increasingly recognizing proteases and their inhibitors as pivotal regulators of vascular function, extending well beyond their established roles in coagulation and matrix degradation. A growing body of experimental and translational research demonstrates that protease activity modulates key aspects of vascular health—affecting endothelial integrity, vascular tone, barrier permeability, and immune–vascular communication. Dysregulation of protease pathways is implicated in a spectrum of cardiovascular and vascular conditions, including sepsis, inflammatory vasculopathies, ischemia–reperfusion injury, thrombosis, and microvascular dysfunction. Yet, despite the centrality of protease-driven mechanisms, research within this domain remains fragmented across several biomedical disciplines, limiting the cross-fertilization of ideas and the translation of mechanistic knowledge into innovative therapy.

This Research Topic aims to bridge basic mechanistic insights and translational advancements by highlighting the dual roles of proteases and protease inhibitors in both vascular dysfunction and reparative processes. The main goal is to spur a discussion on how controlled proteolysis drives not only pathological changes such as endothelial injury, inflammation, and coagulopathy, but also adaptive vascular remodeling, angiogenesis, and restoration of endothelial barrier function post-injury. By exploring the therapeutic potential of endogenous and pharmacological protease inhibitors—especially within the context of cardiovascular biologics and regenerative strategies—the initiative seeks to move beyond traditional views of proteases as purely deleterious, illuminating their nuanced roles as modulators of vascular repair and homeostasis.

To gather further insights into the diverse functions and translational impact of proteases and their inhibitors in vascular health and disease, we welcome articles addressing, but not limited to, the following themes:

• Protease signaling in endothelial dysfunction and regulation of vascular permeability

• The role of protease-activated receptors in vascular inflammation and modulation of tone

• Involvement of serine proteases in microvascular dysfunction and vasoplegic syndromes

• Mechanistic crosstalk among protease activity, coagulation, and inflammatory pathways

• Functions of endogenous protease inhibitors in maintaining vascular stability and adaptation

• Therapeutic impacts of protease inhibition beyond classic anticoagulation

• Protease-driven mechanisms in cardiovascular inflammatory states and critical illness

• Contributions of protease activity to vascular remodeling, repair, and angiogenesis

• Translational and clinical studies of biologic protease modulation in vascular pathologies

This Research Topic accepts all article types. The overarching aim is to foster an integrated perspective on protease-based mechanisms and therapeutic interventions, advancing progress in cardiovascular biologics and regenerative medicine.