| First Author | Pendse AA | Year | 2012 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 32 |
| Issue | 6 | Pages | 1436-44 |
| PubMed ID | 22539598 | Mgi Jnum | J:197088 |
| Mgi Id | MGI:5490737 | Doi | 10.1161/ATVBAHA.112.248682 |
| Citation | Pendse AA, et al. (2012) Pro- and antiatherogenic effects of a dominant-negative P465L mutation of peroxisome proliferator-activated receptor-gamma in apolipoprotein E-Null mice. Arterioscler Thromb Vasc Biol 32(6):1436-44 |
| abstractText | OBJECTIVE: The dominant-negative mutation, P467L, in peroxisome proliferator-activated receptor-gamma (PPARgamma) affects adipose tissue distribution, insulin sensitivity, and blood pressure in heterozygous humans. We hypothesized that the equivalent mutation, PPARgamma-P465L, in mice will worsen atherosclerosis. METHODS AND RESULTS: Apolipoprotein E-null mice with and without PPARgamma-P465L mutation were bred in 129S6 inbred genetic background. Mild hypertension and lipodystrophy of PPARgamma-P465L persisted in the apolipoprotein E-null background. Glucose homeostasis was normal, but plasma adiponectin was significantly lower and resistin was higher in PPARgamma-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. PPARgamma-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 PPARgamma-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 PPARgamma-P465L. CONCLUSIONS: Small, competing pro- and antiatherogenic effects of PPARgamma-P465L mutation result in unchanged plaque development in apolipoprotein E-deficient mice. |
