The potential role of serine proteinase inhibitors for the prevention of plaque rupture

The thrombotic cascade interacts with the thrombolytic cascade in a delicate physiological balance that is intended to control clot formation at sites of vascular injury (1-3). Both cascades consist of sequentially activated serine proteinase enzymes that form a catalytic chain. The balance between thrombosis, coagulation (Figs. 1, 2), and thrombolysis (Fig. 3) is thus dependent on the relative activation states of the serine proteinase enzymes in each cascade. The activation of the regulatory steps or enzymes in each cascade is controlled, at least in part, by serine proteinase inhibitors (serpins) that can alter the balance between coagulation and clot lysis (4-7). These interactions of enzyme and serpin in each system may act as the dominant players or simply as background, low-level activity, depending on the current activation states of each cascade, much as two soloists in a duet shift dominance with each other and the chorus throughout a musical composition.