Key result
Ex vivo treatment of human platelets with oxidized LDL and thrombin significantly increased P-selectin expression and MAPK phosphorylation compared to resting controls.
Absolute Event Rate: 34.4% vs 11.29%
p-value: p=0.001
MAPK inhibitors reduce P-selectin expression in platelets activated by oxidative and thrombotic stimuli, highlighting a potential therapeutic target for atherothrombosis.
Suggests MAPK inhibition may blunt oxLDL-thrombin platelet activation; hypothesis-generating for atherothrombosis, no practice change yet.
INTRODUCTION: Atherosclerosis is one of the inflammatory underlying disease associated by oxidative stress and thrombotic agents. This study aimed to evaluate the potential role of cupper oxidized low-density lipoprotein (OxLDL) and thrombin for inducing mitogen activated protein kinases (MAPKs) in platelets. METHODS: Phosphorylation of P38MAPK, Jun N-terminal Kinase (JNK), and Extracellular signal-regulated kinases (ERK1/2) and P-selectin expression were determined in lysates of washed human platelets pretreated with low doses of thrombin and cu2+-OxLDL By Enzyme-linked immunosorbent assay (ELISA). Pharmacological inhibition was performed by SB203580, PD980559 and SP6000125 for P38MAPK, ERK1/2 and JNK activity, respectively. The ratio of phosphorylated to total protein was used for normalizing the phospho proteins contents of cells. RESULTS: OxLDL and thrombin significantly and differentially increased P-selectin expression (P<0.05), P38MAPK (P<0.05) and c-JNK (P<0.05) and ERK1/2 (P<0.05) phosphorylation in platelets. SB 203580 and SP6000125 significantly decreased P-selectin expression in both oxidative (P<0.05) and thrombotic (P<0.05) activated platelets. CONCLUSION: Our results indicated that MAPK inhibitors can reduce atherothrombotic events via alterations in P-selectin expression suggesting that these inhibitors may be useful in the inhibition of atheroma development.
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Karimi et al. (2013) studied Healthy (n=90). Oxidized LDL and Thrombin vs. Resting platelets was evaluated on P-selectin expression (µg/ml) (p=0.001). Ex vivo treatment of human platelets with oxidized LDL and thrombin significantly increased P-selectin expression and MAPK phosphorylation compared to resting controls.
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