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Pro- and antiatherogenic effects of a dominant-negative P465L mutation of peroxisome proliferator-activated receptor-γ in apolipoprotein E-Null mice.

Publication ,  Journal Article
Pendse, AA; Johnson, LA; Kim, H-S; McNair, M; Nipp, CT; Wilhelm, C; Maeda, N
Published in: Arterioscler Thromb Vasc Biol
June 2012

OBJECTIVE: The dominant-negative mutation, P467L, in peroxisome proliferator-activated receptor-γ (PPARγ) affects adipose tissue distribution, insulin sensitivity, and blood pressure in heterozygous humans. We hypothesized that the equivalent mutation, PPARγ-P465L, in mice will worsen atherosclerosis. METHODS AND RESULTS: Apolipoprotein E-null mice with and without PPARγ-P465L mutation were bred in 129S6 inbred genetic background. Mild hypertension and lipodystrophy of PPARγ-P465L persisted in the apolipoprotein E-null background. Glucose homeostasis was normal, but plasma adiponectin was significantly lower and resistin was higher in PPARγ-P465L mice. Plasma cholesterol and lipoprotein distribution were not different, but plasma triglycerides tended to be reduced. Surprisingly, there were no overall changes in the atherosclerotic plaque size or composition. PPARγ-P465L macrophages had a small decrease in CD36 mRNA and a small yet significant reduction in very-low-density lipoprotein uptake in culture. In unloaded apolipoprotein E-null macrophages with PPARγ-P465L, cholesterol uptake was reduced whereas apolipoprotein AI-mediated efflux was increased. However, when cells were cholesterol loaded in the presence of acetylated low-density lipoprotein, no genotype difference in uptake or efflux was apparent. A reduction of vascular cell adhesion molecule-1 expression in aorta suggests a relatively antiatherogenic vascular environment in mice with PPARγ-P465L. CONCLUSIONS: Small, competing pro- and antiatherogenic effects of PPARγ-P465L mutation result in unchanged plaque development in apolipoprotein E-deficient mice.

Duke Scholars

Published In

Arterioscler Thromb Vasc Biol

DOI

EISSN

1524-4636

Publication Date

June 2012

Volume

32

Issue

6

Start / End Page

1436 / 1444

Location

United States

Related Subject Headings

  • Vascular Cell Adhesion Molecule-1
  • Triglycerides
  • Time Factors
  • Resistin
  • Phenotype
  • PPAR gamma
  • Mutation
  • Mice, Knockout
  • Mice, 129 Strain
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Pendse, A. A., Johnson, L. A., Kim, H.-S., McNair, M., Nipp, C. T., Wilhelm, C., & Maeda, N. (2012). Pro- and antiatherogenic effects of a dominant-negative P465L mutation of peroxisome proliferator-activated receptor-γ in apolipoprotein E-Null mice. Arterioscler Thromb Vasc Biol, 32(6), 1436–1444. https://doi.org/10.1161/ATVBAHA.112.248682
Pendse, Avani A., Lance A. Johnson, Hyung-Suk Kim, Marcus McNair, C Taylor Nipp, Carolyn Wilhelm, and Nobuyo Maeda. “Pro- and antiatherogenic effects of a dominant-negative P465L mutation of peroxisome proliferator-activated receptor-γ in apolipoprotein E-Null mice.Arterioscler Thromb Vasc Biol 32, no. 6 (June 2012): 1436–44. https://doi.org/10.1161/ATVBAHA.112.248682.
Pendse AA, Johnson LA, Kim H-S, McNair M, Nipp CT, Wilhelm C, et al. Pro- and antiatherogenic effects of a dominant-negative P465L mutation of peroxisome proliferator-activated receptor-γ in apolipoprotein E-Null mice. Arterioscler Thromb Vasc Biol. 2012 Jun;32(6):1436–44.
Pendse, Avani A., et al. “Pro- and antiatherogenic effects of a dominant-negative P465L mutation of peroxisome proliferator-activated receptor-γ in apolipoprotein E-Null mice.Arterioscler Thromb Vasc Biol, vol. 32, no. 6, June 2012, pp. 1436–44. Pubmed, doi:10.1161/ATVBAHA.112.248682.
Pendse AA, Johnson LA, Kim H-S, McNair M, Nipp CT, Wilhelm C, Maeda N. Pro- and antiatherogenic effects of a dominant-negative P465L mutation of peroxisome proliferator-activated receptor-γ in apolipoprotein E-Null mice. Arterioscler Thromb Vasc Biol. 2012 Jun;32(6):1436–1444.

Published In

Arterioscler Thromb Vasc Biol

DOI

EISSN

1524-4636

Publication Date

June 2012

Volume

32

Issue

6

Start / End Page

1436 / 1444

Location

United States

Related Subject Headings

  • Vascular Cell Adhesion Molecule-1
  • Triglycerides
  • Time Factors
  • Resistin
  • Phenotype
  • PPAR gamma
  • Mutation
  • Mice, Knockout
  • Mice, 129 Strain
  • Mice