• Original article (Basic research) • Previous Articles     Next Articles

Correlation between calprotectin, TLR-4, and MAPK signal transduction pathways and COX-2 in the process of arterial thrombosis

CHEN Xiao-nan1, WANG Hong-yan1, ZHAO Hong-yu1, CAO Jiu-mei1, LU Lin2, WU Fang1   

  1. 1.Department of Geriatric, 2.Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
  • Online:2016-04-28 Published:2016-05-26
  • Supported by:

    Foundation of Science and Technology Committee of Shanghai Municipality, 124119a6800; Key Discipline Construction of Public Health in Shanghai, 12GWZX1002


Objective To investigate calprotectin (S100A8/A9), Toll-like receptor 4 (TLR-4), and mitogen-activity of protein kinase (MAPK) signaling pathways in the arteries thrombosis and their correlation with cyclooxygenase-2 (COX-2). Methods Twenty-four SD rats were assigned to the experiment group and the control group. A rat model of carotid artery thrombosis was constructed in the experiment group by using FeCl3 solution. The same volume of normal saline was injected in the control group. Rats were sacrificed at the 1st, 3rd, 7th, and 14th day after the model was constructed and 3 rats per group were sacrificed each time. S100A8/A9 level in peripheral blood was measured by ELISA. Western blotting was used to detect COX-2, p-p38 MAPK, and TLR-4 levels in peripheral blood leukocytes. Then the correlation between these factors was analyzed. MAPK inhibitor SB203580 was used to intervene the rat model and the effects on COX-2 protein level was observed. Results For the experiment group, the S100A8/A9 level in rat peripheral blood reached the peak at the 7th day after the model was constructed, fell at the 14th day, and was significantly higher as compared with the control group at corresponding time points (P<0.05). The expressions of TLR-4, p-p38 MAPK, and COX-2 in peripheral blood leukocytes increased with time after the model was constructed and reached peak at the 14th day. The correlation between TLR-4 and COX-2 was close (r=0.831, P=0.012). After intervention with MAPK inhibitors, the protein level of COX-2 significantly reduced. Conclusion S100A8/A9 may mainly participate in the early inflammation response process in arteriogenesis. COX-2 has a certain correlation with TLR-4 in terms of protein expression. At the early stage of arterial thrombosis, elevated COX-2 expression may be associated with TLR-4/p38 MAPK signaling pathway activated by high level of S100A8/A9.

Key words: thrombotic diseases, cyclooxygenase-2, calprotectin, Toll-like receptors, mitogen-activated protein kinase