Intimal smooth muscle cells up-regulate β-very low density lipoprotein-mediated cholesterol accumulation by enhancing β-very low density lipoprotein uptake and decreasing cholesterol efflux

Itsuko Ishii, Hidemi Satoh, Hirokazu Kawachi, Hisato Jingami, Naoki Matsuoka, Shigeru Ohmori, Hideaki Bujo, Tokuo Yamamoto, Yasushi Saito, Mitsukazu Kitada

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

To clarify the mechanism of smooth muscle cell (SMC)-derived foam cell formation, we investigated β-very low density lipoprotein (β-VLDL) cholesterol metabolism in vascular medial SMCs (M-SMCs) from normal rabbits compared with intimal SMCs (I-SMCs) from normal rabbits fed a high-cholesterol diet and LDL receptor-deficient rabbits. For both types of I-SMCs, uptake of [3H]cholesteryl oleate labeled β-VLDL increased 1.6 times and release of [3H]cholesterol decreased 40% compared with M-SMCs. M-SMCs took up part of the β-VLDL through the LDL receptor but I-SMCs did not. mRNAs for the VLDL receptor and the LDL receptor relative with 11 ligand binding repeats were expressed at similar levels in all SMCs. M-SMCs expressed more LDL receptor-related protein than I-SMCs. Ligand blotting analysis revealed greater 125I-β-VLDL binding to a 700-kDa protein in I-SMCs compared with M-SMCs. I-SMCs had higher activities of acid cholesterol esterase and acyl-CoA:cholesterol acyltransferase, and lower activity of neutral cholesterol esterase than M-SMCs in both the absence and the presence of β-VLDL. These results indicate that I-SMCs accumulate more cholesteryl ester than M-SMCs by taking up more β-VLDL and by effluxing less cholesterol.

Original languageEnglish
Pages (from-to)30-38
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1585
Issue number1
DOIs
Publication statusPublished - 2002 Nov 8

Keywords

  • Foam cell formation
  • LDL receptor
  • LR11
  • VLDL receptor
  • Vascular smooth muscle cell

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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