Review ArticlesPlasma Kallikrein Inhibitors in Cardiovascular Disease An Innovative Therapeutic ApproachKolte, Dhaval MD, PhD; Shariat-Madar, Zia PhDAuthor Information From the *Department of Medicine, New York Medical College, Valhalla, NY; and †Department of Pharmacology, School of Pharmacy, University of Mississippi, University, MS. Disclosure: The authors have no conflicts of interest to report. Correspondence: Dhaval Kolte, MD, PhD, Department of Medicine, Taylor Pavilion, New York Medical College, Valhalla, NY 10595. E-mail: [email protected]. Cardiology in Review: May/June 2016 - Volume 24 - Issue 3 - p 99-109 doi: 10.1097/CRD.0000000000000069 Buy Metrics Abstract Plasma prekallikrein is the liver-derived precursor of the trypsin-like serine protease plasma kallikrein, and circulates in plasma bound to high molecular weight kininogen. Plasma prekallikrein is activated to plasma kallikrein by activated factor XII or prolylcarboxypeptidase. Plasma kallikrein regulates the activity of multiple proteolytic cascades in the cardiovascular system such as the intrinsic pathway of coagulation, the kallikrein–kinin system, the fibrinolytic system, the renin–angiotensin system, and the complement pathways. As such, plasma kallikrein plays a central role in the pathogenesis of thrombosis, inflammation, and blood pressure regulation. Under physiological conditions, plasma kallikrein serves as a cardioprotective enzyme. However, its increased plasma concentration or hyperactivity perpetuates cardiovascular disease (CVD). In this article, we review the biochemistry and cell biology of plasma kallikrein and summarize data from preclinical and clinical studies that have established important functions of this serine protease in CVD states. Finally, we propose plasma kallikrein inhibitors as a novel class of drugs with potential therapeutic applications in the treatment of CVDs. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.