Tyrosine kinase dependent lectin-like oxidized LDL receptor-1 upregulation by thrombin and factor Xa in vascular smooth muscle cells / 中华心血管病杂志

ABSTRACT

<p><b>OBJECTIVE</b>Thrombin and factor Xa are key players in the process of arterial thrombi formation and lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) is a cell surface endocytosis receptor for atherogenic oxidized LDL (ox-LDL). Here we investigate whether thrombin and factor Xa can induce LOX-1 protein expressions in cell-associated forms and soluble forms in cultured bovine aortic smooth muscle cells (BSMCs).</p><p><b>METHODS</b>BSMCs were treated with thrombin or factor Xa in the presence or absence of AG1478, an epidermal growth factor (EGF) receptor-associated tyrosine kinase inhibitor. Total cell lysates and concentrated culture medium were then analyzed by Western blot using a mouse anti-LOX-1 monoclonal antibody.</p><p><b>RESULTS</b>LOX-1 protein levels in cell lysates and culture medium were significantly increased by thrombin and factor Xa in a concentration- and time-dependent manner. Upregulation of LOX-1 protein expressions in cell lysates and concentrated culture medium was observed at concentrations above 2.0 and 3.0 U/ml of thrombin and 50 and 100 nmol/L of factor Xa, respectively. Increased LOX-1 protein expressions in cell lysates and cell culture medium were detectable as early as 4 h and peaked at 12 h after treatment with thrombin or factor Xa. LOX-1 expression induced by thrombin and factor Xa could be blocked by pretreatment with AG1478.</p><p><b>CONCLUSIONS</b>Thrombin and factor Xa can act as LOX-1 inducers via tyrosine kinase activation.</p>