Chylomicron remnants regulate early growth response factor-1 in vascular smooth muscle cells.
Early growth response factor-1 (Egr-1) is a zinc-finger transcription factor that induces genes that promote atherosclerosis. The goal of the present study was to determine whether Egr-1 expression is modulated by atherogenic, triglyceride rich lipoproteins known as chylomicron remnants. Chylomicron remnants induced Egr-1 mRNA and protein expression in rat cultured vascular smooth muscle cells (VSMCs) and activated extracellular signal-regulated kinase (ERK) 1/2 in VSMCs. Further, chylomicron remnant-induced Egr-1 expression was inhibited by PD98059, a selective inhibitor of MAPK kinase (MEK), suggesting that the action of chylomicron remnants on Egr-1 was dependent on the ERK/MEK pathway. Chylomicron remnants also induced mRNA expression of the pro-inflammatory cytokines, IL-2 and IFN-gamma in VSMCs. We conclude that chylomicron remnants act as atherogenic lipoproteins via induction of Egr-1 expression and via cytokine-mediated inflammation.
Takahashi
Yuko
Y
Division of Cardiovascular and Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan.
Fujioka
Yoshio
Y
Takahashi
Tomosaburo
T
Domoto
Koji
K
Takahashi
Akihiro
A
Taniguchi
Takahiro
T
Ishikawa
Yuichi
Y
Yokoyama
Mitsuhiro
M
D000818:Animals; D002478:Cells, Cultured; D053298:Chylomicron Remnants; D002914:Chylomicrons / Q000494:pharmacology / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins / Q000096:biosynthesis* / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics
D053298:Chylomicron Remnants; D002914:Chylomicrons; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D014157:Transcription Factors