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Expression of lectin-like oxidized LDL receptor-1 in smooth muscle cells after vascular injury

Hideyuki Eto1, Masaaki Miyata, Noriaki Kume

  • 1Department of Cardiovascular, Respiratory and Metabolic Medicine, Graduate School of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.

Biochemical and Biophysical Research Communications
|January 26, 2006
PubMed

Insights

Lectin-like oxidized LDL receptor-1 (LOX-1) drives smooth muscle cell proliferation and contributes to neointimal formation after vascular injury. This receptor plays a key role in restenosis following angioplasty.

Area of Science:

  • Cardiovascular Biology
  • Vascular Biology
  • Molecular Medicine

Background:

  • Lectin-like oxidized LDL receptor-1 (LOX-1) is an oxidized LDL receptor.
  • Its specific role in restenosis after angioplasty is not fully understood.

Purpose of the Study:

  • To investigate the role of LOX-1 in neointimal formation and smooth muscle cell proliferation following vascular injury.

Main Methods:

  • Balloon-injury model in rabbit aorta.
  • Reverse transcription-polymerase chain reaction (RT-PCR) for LOX-1 mRNA expression.
  • Immunohistochemistry and in situ hybridization for LOX-1 protein localization.
  • In vitro studies on cultured smooth muscle cells (SMC) with oxidized LDL (ox-LDL) and LOX-1 antisense oligonucleotides.
  • Double immunofluorescence staining for LOX-1 and proliferating cell nuclear antigen (PCNA).

Main Results:

  • LOX-1 mRNA expression peaked 2 days post-injury and remained elevated for 24 weeks.
  • LOX-1 was expressed in medial and neointimal SMCs after injury, but not in non-injured aorta.
  • Low concentrations of ox-LDL stimulated SMC proliferation, which was inhibited by LOX-1 antisense oligonucleotides.
  • LOX-1 colocalized with PCNA in human restenotic lesions.

Conclusions:

  • LOX-1 mediates ox-LDL-induced SMC proliferation.
  • LOX-1 plays a significant role in neointimal formation after vascular injury.
  • Targeting LOX-1 may be a therapeutic strategy for preventing restenosis.

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