Modified atherogenic lipoproteins induce expression of pentraxin-3 by human vascular smooth muscle cells.
Inflammation is a critical contributing factor to the development and the progression of atherosclerosis. Recently, the acute-phase protein pentraxin-3 (PTX3), which has C-terminal sequence homology with the classic pentraxin C-reactive protein (CRP), was described to be increased in patients with myocardial infarction. In this study, we have investigated the capacity of human primary vascular smooth muscle cells (VSMC), derived from arterial specimens of ten different patients, to express PTX3 after incubation with atherogenic lipoproteins. Enzymatically degraded LDL (E-LDL), which is present in human early lesions, mediated a rapid cholesterol loading and foam cell transformation of primary VSMC, which was paralleled by a marked dose- and time-dependent expression of PTX3 mRNA and release of the acute-phase protein. Expression of PTX3 mRNA was delayed and remained almost undetectable for up to 6 h of incubation with E-LDL. However, during extended exposure to E-LDL for more than 24 h, PTX3 mRNA expression increased by more than 15-fold in VSMC foam cells, which was reflected by a concomitant release of up to 211 ng/ml PTX3 protein. We provide evidence for marked expression of PTX3 by VSMC induced by degraded lipoproteins, which may lead to an in situ vascular acute-phase reaction, contributing to the inflammatory pathogenesis of atherosclerosis.
Klouche
Mariam
M
Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Franz-Josef-Strauss Allee 11 93053 Regensburg, Germany. mariam.klouche@klink.uni-regensburg.de
Peri
Giuseppe
G
Knabbe
Cornelius
C
Eckstein
Hanns-Henning
HH
Schmid
Franz-Xaver
FX
Schmitz
Gerd
G
Mantovani
Alberto
A
D000210:Acute-Phase Reaction / Q000209:etiology; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000150:complications / Q000378:metabolism*; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism*; D018929:Cell Culture Techniques; D005487:Foam Cells / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D000683:Serum Amyloid P-Component / Q000235:genetics / Q000378:metabolism*; D000099153:Pentraxins
D002097:C-Reactive Protein; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D000683:Serum Amyloid P-Component; D000099153:Pentraxins