Affiliation:
1. From the Departments of Internal Medicine and Physiology (H.C., D.L., J.L.M.), University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, Arkansas; and the Department of Surgical Sciences (T.S.), University of Uppsala, Sweden.
Abstract
Oxidatively modified LDL (ox-LDL) activates a lectin-like receptor, LOX-1, which results in the expression of adhesion molecules on endothelial surface. We investigated the regulation of the expression of transforming growth factor-β
1
(TGF-β
1
) and its receptors by ox-LDL and the functional significance of this interaction with regard to adhesion molecule expression in human coronary artery endothelial cells (HCAECs). Ox-LDL, in a time- and concentration-dependent manner, upregulated the expression of all 3 subtypes (1, 2, and 3 [including endoglin]) of TGF-β
1
receptors and decreased active TGF-β
1
synthesis (all
P
<0.05 versus control and native-LDL–treated cells). Treatment of HCAECs with a monoclonal antibody to LOX-1 attenuated ox-LDL–mediated upregulation of TGF-β
1
receptors and decrease in TGF-β
1
synthesis (
P
<0.05 versus ox-LDL alone). Ox-LDL also enhanced the expression of P-selectin and ICAM-1 as well as monocyte adhesion to HCAECs (
P
<0.05 versus control untreated cells). Pretreatment with recombinant TGF-β
1
attenuated the enhanced expression of adhesion molecules and monocyte adhesion to HCAECs (
P
<0.05 versus ox-LDL alone). Effects of recombinant TGF-β
1
were blocked by antibody to TGF-β
1
receptor type 2, but not by antibody to endoglin. Thus ox-LDL, via activation of LOX-1, increases the expression of TGF-β
1
receptors and decreases TGF-β
1
synthesis in HCAECs. Recombinant TGF-β
1
, by binding to TGF-β
1
type 2 receptors, modulates ox-LDL–mediated expression of adhesion molecules and monocyte adhesion to HCAECs.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine,Physiology
Cited by
57 articles.
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