Kallikrein-kinin system (KKS) (KKS)

The Kallikrein-kinin system (KKS) is a complex metabolic pathway that produces vasoactive peptides, primarily bradykinin and kallidin, which play critical roles in cardiovascular homeostasis and inflammation [1]. The system is initiated by the activation of factor XII or tissue kallikreins, leading to the proteolytic cleavage of kininogens by kallikrein enzymes [2]. These kinins exert their biological effects through two G protein-coupled receptors: the constitutively expressed B2 receptor and the injury-inducible B1 receptor [3]. Activation of these receptors results in potent vasodilation, increased vascular permeability, and the mediation of pain and inflammatory responses [4]. Dysregulation of the KKS is implicated in various pathologies, most notably hereditary angioedema (HAE), where uncontrolled bradykinin production leads to life-threatening swelling [5]. Therapeutic strategies targeting this system include plasma kallikrein inhibitors and B2 receptor antagonists, which are used to manage acute attacks and provide prophylaxis in HAE [6]. Additionally, the system's interaction with the renin-angiotensin system via ACE makes it a focal point for blood pressure management and potential side effects like ACE inhibitor-induced angioedema [7].

Other names

Kinin systemKinin-kallikrein systemContact activation systemPlasma kallikrein-kinin system

Inhibition of plasma kallikrein to prevent the release of bradykinin from high-molecular-weight kininogen; antagonism of bradykinin B2 receptors to block downstream signaling; inhibition of angiotensin-converting enzyme (ACE) to prevent the degradation of kinins.