Chemokine CC-motif ligand 2 participates in platelet function and arterial thrombosis by regulating PKCα-P38MAPK-HSP27 pathway
Autor: | Xiaoxiang Tian, Yu Cao, Dan Liu, Yaling Han, Chengfei Peng, Xiaolin Zhang, Meili Liu, Yanxia Liu, Chenghui Yan |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Blood Platelets Male CCR2 Chemokine Protein Kinase C-alpha Platelet Aggregation SB 203580 Receptors CCR2 HSP27 Heat-Shock Proteins Inflammation 030204 cardiovascular system & hematology Pharmacology CCL2 p38 Mitogen-Activated Protein Kinases 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine medicine Animals Humans Platelet Platelet activation Phosphorylation Molecular Biology Protein Kinase Inhibitors Chemokine CCL2 Heat-Shock Proteins Aged Mice Knockout biology Thrombosis Middle Aged Platelet Activation Disease Models Animal 030104 developmental biology Carotid Arteries chemistry biology.protein Molecular Medicine ST Elevation Myocardial Infarction Female Signal transduction medicine.symptom Molecular Chaperones Signal Transduction |
Zdroj: | Biochimica et biophysica acta. Molecular basis of disease. 1864(9 Pt) |
ISSN: | 0925-4439 |
Popis: | Background Studies indicate that chemokine CC-motif ligand 2 (CCL2) is involved in inflammation and atherosclerosis. However, the roles and mechanisms of CCL2 on platelet function and arterial thrombosis are unknown. Methods The expressions of CCL2 or CCR2 in the plasma, platelets and coronary thrombus of ST-elevated myocardial infarction (STEMI) patients were examined by ELISA, Western blot, immunohistochemistry and immunofluorescence. The roles of CCL2 on platelet aggregation, activation and secretion were examined by light transmission aggregometry, flow cytometry and ELISA. Results The expressions of CCL2 or CCR2 in the plasma or platelets of STEMI patients with platelet high response were higher than those with platelet normal response; In vitro, exogenous recombinant human CCL2 markedly increased platelet aggregation, activation and granule secretion, which were abolished by CCL2 neutralizing antibody or CCR2 inhibiter. CCL2 increased the phosphorylation levels of PKCα (Thr638), P38MAPK (Thr180/Tyr182) and HSP27 (S78/S82) in human platelets, which were abrogated by PKCα inhibitor (RO 318220) or P38MAPK inhibitor (SB 203580). RO 318220 or SB 203580 diminished CCL2-induced platelet function. In CCL2 −/− mice, platelet aggregation and secretion were attenuated; the phosphorylation of PKCα, P38MAPK and HSP27 were decreased. In a carotid arterial thrombus mouse model, CCL2 −/− mice displayed a significantly extended carotid artery occlusion time compared with wild type. Conclusions CCL2 played important roles in regulating platelet function and arterial thrombosis through the PKCα-P38MAPK-HSP27 pathway, which might provide theoretical basis for searching new antiplatelet drugs and the treatment for cardiovascular diseases. |
Databáze: | OpenAIRE |
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