Antiplatelet strategies: past, present, and future.

Antiplatelet therapy plays a critical role in the prevention and treatment of major cardiovascular diseases triggered by thrombosis. Since the 1900s, significant progress in reducing morbidity and death caused by cardiovascular diseases has been made. However, despite the development and approval of drugs that specifically target the platelet, including inhibitors for cycloxygenase-1, P2Y receptor, integrin αIIbβ3, phosphodiesterases, and protease-activated receptor 1, the risk of recurrent thrombotic events remains high, and the increased risk of bleeding is a major concern.

Investigating the catalytic efficiency of C22-Fatty acids with LOX human isozymes and the platelet response of the C22-oxylipin products.

Polyunsaturated fatty acids (PUFAs) have been extensively studied for their health benefits because they can be oxidized by lipoxygenases to form bioactive oxylipins. In this study, we investigated the impact of double bond placement on the kinetic properties and product profiles of human platelet 12-lipoxygenase (h12-LOX), human reticulocyte 15-lipoxygenase-1 (h15-LOX-1), and human endothelial 15-lipoxygenase-2 (h15-LOX-2) by using 22-carbon (C22) fatty acid substrates with differing double bond content. With respect to k/K values, the loss of Δ and Δ led to an 18-fold loss of kinetic activity for h12-LOX, no change in kinetic capability for h15-LOX-1, but a 24-fold loss for h15-LOX-2 for both C22-FAs.

The oxylipin analog CS585 prevents platelet activation and thrombosis through activation of the prostacyclin receptor.

Cardiovascular disease remains the primary cause of morbidity and mortality globally. Platelet activation is critical for maintaining hemostasis and preventing the leakage of blood cells from the vessel. There has been a paucity in the development of new drugs to target platelet reactivity.

Bioactive lipid regulation of platelet function, hemostasis, and thrombosis.

Platelets are small, anucleate cells in the blood that play a crucial role in the hemostatic response but are also implicated in the pathophysiology of cardiovascular disease. It is widely appreciated that polyunsaturated fatty acids (PUFAs) play an integral role in the function and regulation of platelets. PUFAs are substrates for oxygenase enzymes cyclooxygenase-1 (COX-1), 5-lipoxygenase (5-LOX), 12-lipoxygenase (12-LOX) and 15-lipoxygenase (15-LOX).

Experimental venous thrombus resolution is driven by IL-6 mediated monocyte actions.

Deep venous thrombosis and residual thrombus burden correlates with circulating IL-6 levels in humans. To investigate the cellular source and role of IL-6 in thrombus resolution, Wild type C57BL/6J (WT), and IL-6 mice underwent induction of VT via inferior vena cava (IVC) stenosis or stasis. Vein wall (VW) and thrombus were analyzed by western blot, immunohistochemistry, and flow cytometry.