当前位置： SCI文献检索 > CIRCULATION期刊下所有文献 > Mildly oxidized LDL induces activation of platelet-derived growth factor beta-receptor pathway.

Mildly oxidized LDL induces activation of platelet-derived growth factor beta-receptor pathway.

Abstract：

BACKGROUND:Mildly oxidized LDL (moxLDL) is thought to play a role in atherogenesis. MoxLDL induces derivatization of cell proteins and triggers a variety of intracellular signaling. We aimed to investigate whether moxLDL-induced protein derivatization may influence the activity of platelet-derived growth factor receptor beta (PDGFRbeta), a tyrosine kinase receptor of major importance in vascular biology and atherogenesis. METHODS AND RESULTS:In cultured rabbit arterial smooth muscle cells, moxLDL induces activation of the PDGFRbeta signaling pathway, as shown by PDGFRbeta tyrosine phosphorylation on Western blot and coimmunoprecipitation of SH2-containing proteins. The cellular events involved in the moxLDL-induced PDGFRbeta activation can be summarized as follows. Oxidized lipids from moxLDL trigger two phases of PDGFRbeta activation involving two separate mechanisms, as shown by experiments on cultured cells (in situ) and on immunopurified PDGFRbeta (in vitro): (1) the first phase may be mediated by 4-hydroxynonenal, which induces PDGFRbeta adduct formation and subsequent PDGFRbeta activation (antioxidant-insensitive step); (2) the second phase involves ceramide-mediated generation of H(2)O(2) (these steps being inhibited by tosylphenylalanylchloromethylketone, an inhibitor of ceramide formation, and by antioxidant BHT, exogenous catalase, or overexpressed human catalase). Because 4-hydroxynonenal-PDGFRbeta adducts are also detected in atherosclerotic aortas, it is suggested that this novel mechanism of moxLDL-induced PDGFRbeta activation may occur during atherogenesis. CONCLUSIONS:MoxLDL acts as a local autoparacrine mediator in the vascular wall, and PDGFRbeta acts as a sensor for both oxidized lipids and oxidative stress. This constitutes a novel mechanism of PDGFRbeta activation in atherosclerotic areas.

journal_name

Circulation

journal_title

Circulation

authors

Escargueil-Blanc I,Salvayre R,Vacaresse N,Jürgens G,Darblade B,Arnal JF,Parthasarathy S,Nègre-Salvayre A

doi

10.1161/hc4001.097179

subject

Has Abstract

pub_date

2001-10-09 00:00:00

pages

1814-21

issue

eissn

0009-7322

issn

1524-4539

journal_volume

104

pub_type

杂志文章

在线工具

Mildly oxidized LDL induces activation of platelet-derived growth factor beta-receptor pathway.