Bradykinin B2 Receptor: A Key Therapeutic Target in Immunological and Vascular Diseases, Driven by Kinin Biology

Bradykinin, a potent nonapeptide, mediates vasoactive and proinflammatory effects primarily through the constitutively expressed bradykinin B2 receptor. Dysregulation of the kinin-kallikrein system, often initiated by Factor XII activation, is implicated in various conditions including angioedema, allergic mast cell-mediated skin diseases, and cardiovascular pathologies. For conditions like Hereditary Angioedema (HAE), current prophylactic treatments often provide insufficient disease control, highlighting a significant unmet therapeutic need. Understanding the precise roles of kinins and their receptors, especially the B2 receptor, is crucial for developing novel, targeted therapies to address these bradykinin-mediated diseases.

This comprehensive review synthesized current knowledge on the biology, regulation, and functions of kinins and their receptors, focusing on bradykinin and the bradykinin B2 receptor. It explored emerging evidence on diverse mechanisms of bradykinin formation and its relevance in disease pathogenesis. The primary objective was to consolidate clinical evidence on the roles of bradykinin and the B2 receptor across various conditions, identifying potential novel therapeutic strategies targeting the bradykinin B2 receptor for managing bradykinin-mediated diseases.

The review established that bradykinin, a key kinin peptide, primarily exerts its vasoactive and proinflammatory effects via the constitutively expressed bradykinin B2 receptor. While the B1 receptor is inducible, the B2 receptor is central to the physiological and pathological actions of bradykinin. > The synthesis of clinical evidence strongly implicates kinins, particularly through bradykinin B2 receptor activation, in the pathogenesis of multiple types of angioedema, as well as allergic mast cell-mediated skin diseases, and various cardiovascular and respiratory pathologies. The authors highlighted that kinin generation is mainly driven by the contact system and plasma/tissue kallikreins, but additional independent cascades also contribute to their formation. This complex biology underscores the broad involvement of the bradykinin B2 receptor in diverse immunological and vascular disease processes, positioning it as a critical therapeutic target.