Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel
Journal cover image

Toxicity of oxidized low density lipoproteins for vascular smooth muscle cells and partial protection by antioxidants.

Publication ,  Journal Article
Guyton, JR; Lenz, ML; Mathews, B; Hughes, H; Karsan, D; Selinger, E; Smith, CV
Published in: Atherosclerosis
December 1995

Oxidized low density lipoprotein (oxLDL) is known to be toxic to a variety of cell types, but relatively little is known about the toxic effects of oxLDL on vascular smooth muscle cells (SMC). We found that LDL oxidized by incubation with 5 microM cupric ions was toxic to cultured porcine SMC when administered at concentrations of 25 micrograms protein/ml and higher. The toxicity was demonstrated whether cells were proliferating or not, and was more evident in the presence of 0.4% lipoprotein-deficient serum than in 10%. Because of recent evidence that 7-ketocholesterol and 7-hydroxycholesterol are toxic species in copper-oxidized LDL, inhibition of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase was hypothesized as a mechanism of toxicity. However, mevalonic acid, the product of this enzyme, failed to protect against the toxicity of either oxLDL or the pure oxysterols. Alpha-tocopherol, alpha-tocopherol acetate, probucol, butylated hydroxytoluene, and deferoxamine provided partial protection to SMC exposed to oxLDL. These results suggested a toxic role for newly initiated lipid peroxidation, either in cells or in media oxLDL. Cellular lipid peroxidation appeared more likely, since no further oxidation of media oxLDL was demonstrated in the presence or absence of antioxidants. Overall, the results suggest that toxicity of copper-oxidized LDL for SMC is multifactorial and differs from the previously described toxicity of iron-oxidized LDL for fibroblasts.

Duke Scholars

Published In

Atherosclerosis

DOI

ISSN

0021-9150

Publication Date

December 1995

Volume

118

Issue

2

Start / End Page

237 / 249

Location

Ireland

Related Subject Headings

  • Vitamin E
  • Thiobarbituric Acid Reactive Substances
  • Swine
  • Probucol
  • Oxidation-Reduction
  • Muscle, Smooth, Vascular
  • Mevalonic Acid
  • Lovastatin
  • Lipoproteins, LDL
  • Lipid Peroxidation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Guyton, J. R., Lenz, M. L., Mathews, B., Hughes, H., Karsan, D., Selinger, E., & Smith, C. V. (1995). Toxicity of oxidized low density lipoproteins for vascular smooth muscle cells and partial protection by antioxidants. Atherosclerosis, 118(2), 237–249. https://doi.org/10.1016/0021-9150(95)05610-6
Guyton, J. R., M. L. Lenz, B. Mathews, H. Hughes, D. Karsan, E. Selinger, and C. V. Smith. “Toxicity of oxidized low density lipoproteins for vascular smooth muscle cells and partial protection by antioxidants.Atherosclerosis 118, no. 2 (December 1995): 237–49. https://doi.org/10.1016/0021-9150(95)05610-6.
Guyton JR, Lenz ML, Mathews B, Hughes H, Karsan D, Selinger E, et al. Toxicity of oxidized low density lipoproteins for vascular smooth muscle cells and partial protection by antioxidants. Atherosclerosis. 1995 Dec;118(2):237–49.
Guyton, J. R., et al. “Toxicity of oxidized low density lipoproteins for vascular smooth muscle cells and partial protection by antioxidants.Atherosclerosis, vol. 118, no. 2, Dec. 1995, pp. 237–49. Pubmed, doi:10.1016/0021-9150(95)05610-6.
Guyton JR, Lenz ML, Mathews B, Hughes H, Karsan D, Selinger E, Smith CV. Toxicity of oxidized low density lipoproteins for vascular smooth muscle cells and partial protection by antioxidants. Atherosclerosis. 1995 Dec;118(2):237–249.
Journal cover image

Published In

Atherosclerosis

DOI

ISSN

0021-9150

Publication Date

December 1995

Volume

118

Issue

2

Start / End Page

237 / 249

Location

Ireland

Related Subject Headings

  • Vitamin E
  • Thiobarbituric Acid Reactive Substances
  • Swine
  • Probucol
  • Oxidation-Reduction
  • Muscle, Smooth, Vascular
  • Mevalonic Acid
  • Lovastatin
  • Lipoproteins, LDL
  • Lipid Peroxidation