In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 23, No. 5 ( 2003-05), p. 816-821
Abstract:
Background— Despite increasing appreciation that atherogenesis involves participation of inflammatory cells, information on mediators of communication between different constituents of atherosclerotic plaque remain incomplete. We examined the role of LOX-1, a receptor for oxidized (ox) LDL, in the expression of CD40/CD40L in cultured human coronary artery endothelial cells (HCAECs). Methods and Results— We observed that ox-LDL increased the expression of CD40 and CD40L in a concentration (10 to 80 μg/mL)- and time (1 to 24 hours)- dependent manner. These effects of ox-LDL were mediated by activation of LOX-1, because pretreatment of HCAECs with a blocking antibody to LOX-1 (JTX92) prevented the expression of CD40 and CD40L in response to ox-LDL ( P 〈 0.01). In parallel experiments, HCAECs were incubated with the protein kinase C (PKC) inhibitor bisindolylmaleimide I, and the cells were then exposed to ox-LDL. Both LOX-1 antibody and the PKC inhibitor inhibited PKC activation in response to ox-LDL ( P 〈 0.01). The PKC inhibitor also blocked the effects of ox-LDL on the expression of CD40 and CD40L ( P 〈 0.01). In additional experiments, we found that it is the PKCα, but not PKCβ and PKCγ, isoform that mediated ox-LDL–induced CD40 and CD40L upregulation. Further experiments showed that upregulation of CD40 mediated induction of proinflammatory genes, because CD40 antibody markedly reduced ox-LDL–induced TNF-α generation and P-selectin expression, whereas nonspecific mouse IgG had no effect. Conclusions— These findings indicate that ox-LDL through its receptor LOX-1 triggers the CD40/CD40L signaling pathway that activates the inflammatory reaction in HCAECs. These observations provide novel insight into ox-LDL–mediated inflammation in atherosclerosis.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/01.ATV.0000066685.13434.FA
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2003
detail.hit.zdb_id:
1494427-3
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