Apolipoprotein D Inhibits Platelet-Derived Growth Factor-BB-Induced Vascular Smooth Muscle Cell Proliferated by Preventing Translocation of Phosphorylated Extracellular Signal Regulated Kinase 1/2 to the Nucleus

Jennifer M. Sarjeant, Allan Lawrie, Caroline Kinnear, Shmuel Yablonsky, Wesley Leung, Hamid Massaeli, Wendy Prichett, John P. Veinot, Eric Rassart, Marlene Rabinovitch

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Objective-Elevated apolipoprotein D (apoD) levels are associated with reduced proliferation of cancer cells. We therefore investigated whether apoD, which occurs free or associated with HDL, suppresses vascular smooth muscle cell (VSMC) proliferation, which is related to the pathobiology of disease. Methods and Results-Intense immunoreactivity for apoD was observed in human atherosclerotic plaque but not in normal coronary artery. However, an increase in apoD mRNA was seen in quiescent relative to proliferating fetal lamb aortic VSMCs, and in the rat aortic VSMC line (A1O), we demonstrated uptake of apoD from serum. Stable transfection of apoD in A10 cells in the absence of serum did not influence VSMC proliferation assessed by [ 3H]-thymidine incorporation. ApoD, administered at a dose of 100 ng/mL, completely inhibited basal as well as platelet-derived growth factor (PDGF)-BB-induced VSMC proliferation (P<0.01) but had no effect on fibroblast growth factor-induced VSMC proliferation. ApoD did not suppress PDGF-BB or fibroblast growth factor-2-induced phosphorylation of extracellular signal regulated kinase (ERK) 1/2 but selectively inhibited PDGF-BB-mediated ERK1/2 nuclear translocation. Conclusions-Our data suggest that apoD selectively modulates the proliferative response of VSMC to growth factors by a mechanism related to nuclear translocation of ERK1/2.

Original languageEnglish
Pages (from-to)2172-2177
Number of pages6
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume23
Issue number12
DOIs
Publication statusPublished - 1 Dec 2003
Externally publishedYes

Fingerprint

Apolipoproteins D
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Vascular Smooth Muscle
Smooth Muscle Myocytes
Cell Proliferation
Fibroblast Growth Factors
antineoplaston A10
Fibroblast Growth Factor 2
Atherosclerotic Plaques
platelet-derived growth factor BB
Serum
Thymidine
Transfection
Intercellular Signaling Peptides and Proteins
Coronary Vessels
Phosphorylation
Cell Line
Messenger RNA

Keywords

  • Apolipoprotein D
  • Extracellular signal-regulated kinase phosphorylation and nuclear translocation
  • Fibroblast growth factor-2
  • Platelet-derived growth factor-BB
  • Proliferation
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Apolipoprotein D Inhibits Platelet-Derived Growth Factor-BB-Induced Vascular Smooth Muscle Cell Proliferated by Preventing Translocation of Phosphorylated Extracellular Signal Regulated Kinase 1/2 to the Nucleus. / Sarjeant, Jennifer M.; Lawrie, Allan; Kinnear, Caroline; Yablonsky, Shmuel; Leung, Wesley; Massaeli, Hamid; Prichett, Wendy; Veinot, John P.; Rassart, Eric; Rabinovitch, Marlene.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 23, No. 12, 01.12.2003, p. 2172-2177.

Research output: Contribution to journalArticle

Sarjeant, Jennifer M. ; Lawrie, Allan ; Kinnear, Caroline ; Yablonsky, Shmuel ; Leung, Wesley ; Massaeli, Hamid ; Prichett, Wendy ; Veinot, John P. ; Rassart, Eric ; Rabinovitch, Marlene. / Apolipoprotein D Inhibits Platelet-Derived Growth Factor-BB-Induced Vascular Smooth Muscle Cell Proliferated by Preventing Translocation of Phosphorylated Extracellular Signal Regulated Kinase 1/2 to the Nucleus. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2003 ; Vol. 23, No. 12. pp. 2172-2177.
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AU - Lawrie, Allan

AU - Kinnear, Caroline

AU - Yablonsky, Shmuel

AU - Leung, Wesley

AU - Massaeli, Hamid

AU - Prichett, Wendy

AU - Veinot, John P.

AU - Rassart, Eric

AU - Rabinovitch, Marlene

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AB - Objective-Elevated apolipoprotein D (apoD) levels are associated with reduced proliferation of cancer cells. We therefore investigated whether apoD, which occurs free or associated with HDL, suppresses vascular smooth muscle cell (VSMC) proliferation, which is related to the pathobiology of disease. Methods and Results-Intense immunoreactivity for apoD was observed in human atherosclerotic plaque but not in normal coronary artery. However, an increase in apoD mRNA was seen in quiescent relative to proliferating fetal lamb aortic VSMCs, and in the rat aortic VSMC line (A1O), we demonstrated uptake of apoD from serum. Stable transfection of apoD in A10 cells in the absence of serum did not influence VSMC proliferation assessed by [ 3H]-thymidine incorporation. ApoD, administered at a dose of 100 ng/mL, completely inhibited basal as well as platelet-derived growth factor (PDGF)-BB-induced VSMC proliferation (P<0.01) but had no effect on fibroblast growth factor-induced VSMC proliferation. ApoD did not suppress PDGF-BB or fibroblast growth factor-2-induced phosphorylation of extracellular signal regulated kinase (ERK) 1/2 but selectively inhibited PDGF-BB-mediated ERK1/2 nuclear translocation. Conclusions-Our data suggest that apoD selectively modulates the proliferative response of VSMC to growth factors by a mechanism related to nuclear translocation of ERK1/2.

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