Systemic Review of Clot Retraction Modulators

Clot retraction is a process by which platelets cause thrombi to shrink, thus stabilizing the clot. After platelets are activated via inside-out signaling, the glycoprotein αIIbβIII binds to fibrinogen and triggers a cascade of intracellular signals that culminate in actin remodeling, leading to a change in platelet shape. This mechanism is also crucial for wound healing. Although the molecular details of clot retraction are not fully understood, various substances and physiological conditions are known to influence this process. This review summarizes the existing literature on modulators of clot retraction.

Additionally, the review explores compounds from Cudrania tricuspidata, Arctium lappa, and Panax ginseng, which are known to inhibit clot retraction and offer multiple other health benefits. Compounds such as caffeic acid and diindolylmethane, both commonly found in plants and vegetables, also reduce clot retraction. Similarly, all-trans retinoic acid (a derivative of vitamin A), two MAP4K inhibitors, and the chemotherapeutic drug Dasatinib have been shown to diminish clot retraction.

Conversely, the endogenous anticoagulant Protein S (PS) and the matricellular protein secreted modular calcium-binding protein 1 (SMOC1) enhance clot retraction. Most studies investigating the mechanisms of clot retraction modulators focus on the increased phosphorylation of vasodilator-stimulated phosphoprotein and inositol 1,4,5-triphosphate receptor I, as well as the decreased phosphorylation of various phospholipases, such as phospholipase A2 (PLA2) and phosphatidylinositol-specific phospholipase Cγ2 (PLCγ2), c-Jun N-terminal kinase, and phosphoinositide 3-kinases (PI3Ks). Other research has examined the decreased phosphorylation of Sarcoma Family Kinases (SFK) and increased cAMP levels. The modulation of inflammatory markers such as thromboxanes (thromboxane A2 (TXA2) and thromboxane B2 (TXB2)), prostaglandin A2 (PGE2), reactive oxygen species (ROS), and cyclooxygenase (COX) enzyme activity has also been studied.

Furthermore, physiological conditions like pregnancy, fibrinolysis, and the autoimmune condition systemic lupus erythematosus appear to impact clot retraction. These findings highlight the need for more in-depth studies to elucidate the mechanisms of clot retraction modulators ISM001-055 and their effects.