Premium
The oxidized phospholipid POVPC induces MMP3 expression and enhances migration of vascular smooth muscle cells
Author(s) -
Cherepanova Olga A.,
Pidkovka Nataliya A.,
Leitinger Norbert,
Owens Gary K.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.329.2
Subject(s) - mmp3 , vascular smooth muscle , extracellular matrix , western blot , microbiology and biotechnology , matrix metalloproteinase , chemistry , downregulation and upregulation , cd36 , zymography , biology , gene expression , biochemistry , gene , endocrinology , smooth muscle
Oxidized phospholipids (oxPLs) including 1‐palmitoyl‐2‐(5‐oxovaleroyl)‐sn‐glycero‐3‐phosphoholine (POVPC) which are active components of minimally modified low density lipoprotein, are primary stimuli of multiple proatherogenic events. Previously we showed that oxPLs including POVPC induced profound phenotypic switching of vascular smooth muscle cells (VSMCs) including suppression of multiple SMC differentiation marker genes as well as activation of multiple inflammatory genes (Pidkovka et al, 2007, Circ Res). Little is known about the effects of oxPLs on genes that play a key functional role in the synthesis and degradation of extracellular matrix proteins that are critical in plaque formation and/or stability. Real time RT‐PCR, Western blot and Zymography analyses showed the increase of MMP3/stromelysin‐1 mRNA and protein level in cultured VSMCs after treatment with POVPC. Furthermore, POVPC‐induced elevation of MMP3 mRNA level was demonstrated in vivo after application of the pluronic gel containing POVPC to carotid arteries of rats. In addition, we found that POVPC enhances the VSMCs migration and invasion in Boyden chambers. The results provide new insights into the possible contribution of oxPLs to the atherogenesis through matrix degradation via MMP release and VSMCs migration leading to plaque destabilization and rupture. Supported by NIH grants R01 HL 38854, R37HL57353 and P01 HL19242.