Plasma L5 levels are elevated in ischemic stroke patients and enhance platelet aggregation

L5, the most electronegative and atherogenic subfraction of low-density lipoprotein (LDL), induces platelet activation. We hypothesized that plasma L5 levels are increased in acute ischemic stroke patients and examined whether lectin-like oxidized LDL receptor-1 (LOX-1), the receptor for L5 on endothelial cells and platelets, plays a critical role in stroke. Because amyloid β (Aβ) stimulates platelet aggregation, we studied whether L5 and Aβ function synergistically to induce prothrombotic pathways leading to stroke. Levels of plasma L5, serum Aβ, and platelet LOX-1 expression were significantly higher in acute ischemic stroke patients than in controls without metabolic syndrome (P < .01). In mice subjected to focal cerebral ischemia, L5 treatment resulted in larger infarction volumes than did phosphate-buffered saline treatment. Deficiency or neutralizing of LOX-1 reduced infarct volume up to threefold after focal cerebral ischemia in mice, illustrating the importance of LOX-1 in stroke injury. In human platelets, L5 but not L1 (the least electronegative LDL subfraction) induced Aβ release via IB kinase 2 (IKK2). Furthermore, L5+Aβ synergistically induced glycoprotein IIb/IIIa receptor activation; phosphorylation of IKK2, IBα, p65, and c-Jun N-terminal kinase 1; and platelet aggregation. These effects were blocked by inhibiting IKK2, LOX-1, or nuclear factor–B (NF-B). Injecting L5+Aβ shortened tail-bleeding time by 50% (n = 1...

Source: Blood - March 10, 2016 Category: Hematology Authors: Shen, M.-Y., Chen, F.-Y., Hsu, J.-F., Fu, R.-H., Chang, C.-M., Chang, C.-T., Liu, C.-H., Wu, J.-R., Lee, A.-S., Chan, H.-C., Sheu, J.-R., Lin, S.-Z., Shyu, W.-C., Sawamura, T., Chang, K.-C., Hsu, C. Y., Chen, C.-H. Tags: Free Research Articles, Platelets and Thrombopoiesis, Thrombosis and Hemostasis Source Type: research