Differential response of vascular smooth muscle cells to oxidized LDL in mouse strains with different atherosclerosis susceptibility

Toru Miyoshi, Jing Tian, Alan H. Matsumoto, Weibin Shi

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Oxidized low-density lipoprotein (LDL) has numerous atherogenic properties, including induction of inflammatory genes, and vascular smooth muscle cells (VSMC) are involved in the development of atherosclerosis. In this study, we examined whether variations of VSMC in the capacity to oxidize LDL or in response to minimally modified LDL (MM-LDL) constitute a genetic component in atherosclerosis. VSMC were isolated from the aorta of two inbred mouse strains C57BL/6J (B6) and C3H, which differ markedly in susceptibility to atherosclerosis. LDL oxidation was assessed by measuring thiobarbituric acid-reactive substance (TBARS) production. Responses to MM-LDL were evaluated by examining the expression of inflammatory genes involved atherosclerosis, including monocyte chemotactic protein-1 (MCP-1) and vascular cell adhesion molecule-1 (VCAM-1), and an oxidant stress gene, heme oxygenase-1 (HO-1). VSMC from the two strains exhibited a comparable ability to transform native LDL to oxidized LDL, whereas their response to MM-LDL differed markedly. MM-LDL resulted in dramatic induction of MCP-1, VCAM-1, and HO-1 mRNAs in the cells from B6 mice but exerted little effect in cells from C3H mice. MCP-1 and soluble VCAM-1 protein levels in conditioned media were measured by ELISA. B6 cells produced significantly more MCP-1 and VCAM-1 proteins in response to MM-LDL than C3H cells. These data suggest that variation in the response of VSMC to oxidized LDL may contribute to the difference between B6 and C3H mice in atherosclerosis susceptibility.

Original languageEnglish
Pages (from-to)99-105
Number of pages7
JournalAtherosclerosis
Volume189
Issue number1
DOIs
Publication statusPublished - Nov 2006
Externally publishedYes

Fingerprint

Vascular Smooth Muscle
Smooth Muscle Myocytes
Atherosclerosis
Vascular Cell Adhesion Molecule-1
Chemokine CCL2
LDL Lipoproteins
Heme Oxygenase-1
Inbred C3H Mouse
Inbred Strains Mice
Thiobarbituric Acid Reactive Substances
Conditioned Culture Medium
Oxidants
Genes
Aorta
oxidized low density lipoprotein
Proteins
Enzyme-Linked Immunosorbent Assay
Gene Expression
Messenger RNA

Keywords

  • Atherosclerosis
  • Lipoprotein
  • Mice
  • Vascular smooth muscle cell

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Differential response of vascular smooth muscle cells to oxidized LDL in mouse strains with different atherosclerosis susceptibility. / Miyoshi, Toru; Tian, Jing; Matsumoto, Alan H.; Shi, Weibin.

In: Atherosclerosis, Vol. 189, No. 1, 11.2006, p. 99-105.

Research output: Contribution to journalArticle

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