Enzymatically degraded, nonoxidized LDL induces human vascular smooth muscle cell activation, foam cell transformation, and proliferation.

Abstract:

BACKGROUND:Enzymatic, nonoxidative modification transforms LDL to an atherogenic molecule (E-LDL) that activates complement and macrophages and is present in early atherosclerotic lesions. METHODS AND RESULTS:We report on the atherogenic effects of E-LDL on human vascular smooth muscle cells (SMC). E-LDL accumulated in these cells, and this was accompanied by selective induction of monocyte chemotactic protein-1 in the absence of effects on the expression of interleukin (IL)-8, RANTES, or monocyte inflammatory proteins-1alpha and -beta). Furthermore, E-LDL stimulated the expression of gp130, the signal-transducing chain of the IL-6 receptor (IL-6R) family, and the secretion of IL-6. E-LDL invoked mitogenic effects on SMC through 2 mechanisms. First, an autocrine mitogenic circuit involving platelet-derived growth factor and fibroblast growth factor-beta was induced. Second, upregulation of gp130 rendered SMC sensitive to transsignaling through the IL-6/sIL-6R activation pathway. Because E-LDL promoted release of both IL-6 and sIL-6R from macrophages, application of macrophage cell supernatants to prestimulated SMC provoked a pronounced and sustained proliferation of the cells. CONCLUSIONS:E-LDL can invoke alterations in SMC that are characteristic of the evolving atherosclerotic lesion.

journal_name

Circulation

journal_title

Circulation

authors

Klouche M,Rose-John S,Schmiedt W,Bhakdi S

doi

10.1161/01.cir.101.15.1799

subject

Has Abstract

pub_date

2000-04-18 00:00:00

pages

1799-805

issue

15

eissn

0009-7322

issn

1524-4539

journal_volume

101

pub_type

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