The Kallikrein-Kinin System and Cardiovascular Diseases: A Narrative Review

This is a narrative review of the plasma kallikrein-kinin system (KKS) which has an important role in human physiology including the cardiovascular (CV) system. Kallikreins are serine proteases, enzymes that cleave proteins, participating in processes like blood pressure (BP) control, inflammation, and coagulation. Kallistatin is an endogenous kallikrein inhibitor with anti-inflammatory, anti-oxidative, and anti-atherosclerotic properties. Kallikrein controls the activity of several proteolytic cascades in the CV system comprising the intrinsic pathway of coagulation, the KKS, the fibrinolytic system, the renin-angiotensin system (RAS), and the complement pathways. Thus, kallikrein plays a crucial role in the pathogenesis of thrombosis, inflammation, and BP regulation. Plasma kallikrein exerts a cardioprotective role, however, when in high concentration or hyperactive, it perpetuates CV disease. Angiotensin-converting enzyme inhibitors and angiotensin AT1 receptor blockers act on both the RAS and the KKS. Moreover, angiotensin II enhances B1 and B2 bradykinin receptor expression via transcriptional mechanisms. These cross-talks explain why both the RAS and KKS are up-regulated in certain circumstances, whereas in others, both systems go the opposite direction (activated RAS/depressed KKS). As the cross-talks between RAS and KKS play an important role in response to different stimuli, considering these cross-talks may help develop drugs targeting the 2 systems.