Tissue Factor/Factor FVII Complex Inhibitors in Cardiovascular Disease. Are Things Going Well?

Gianluca      Petrillo; Plinio      Cirillo; Greta-      Luana D'Ascoli; Fabio      Maresca; Francesca      Ziviello; Massimo      Chiariello

Abstract

Blood coagulation is a complex biological mechanism aimed to avoid bleeding in which a highly regulated and coordinated interplay of specific proteins and cellular components respond quickly to a vascular injury. However, when this mechanisms occurs in the coronary circulation, it has not a “protective” effect, but rather, it plays a pivotal role in determining acute coronary syndromes. Coagulation recognizes Tissue Factor (TF), the main physiological initiator of the extrinsic coagulation pathway, as its starter. Since TF:VIIa complex is the critical point of the blood coagulation cascade, it is a pharmacological attractive issue for the development of agents with anti thrombotic properties that can exert their activity by inhibiting complex formation and/or its catalytic activity. In fact, it is intuitive that an antithrombotic agent able to inhibit this initial step of the coagulation pathway has several theoretical, extremely important, advantages if compared with drugs active downstream the coagulation pathway, such as FXa or thrombin. The present report gives a brief overview of TF pathophysiology, highlighting the most recent advances in the field of inhibitors of the complex TF/VIIa potentially useful in cardiovascular disease.

Keywords: Blood coagulation, cardiovascular disease, factor VIIa, tissue factor, intracoronary thrombi, circulating blood, proteolysis, multi-step process, TF encryption, coagulation, TF procoagulant activity, Immunohistochemistry, athero-thrombotic risk, discontinuation, DNA transfer, FFR-rFVIIa, PROXIMATE-TIMI 27, Kunitz-type, TFPI-coated, atherosclerotic, FXa, rFVIIai