| First Author | Qu A | Year | 2012 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 32 |
| Issue | 1 | Pages | 65-73 |
| PubMed ID | 22015658 | Mgi Jnum | J:195979 |
| Mgi Id | MGI:5486294 | Doi | 10.1161/ATVBAHA.111.239137 |
| Citation | Qu A, et al. (2012) Disruption of endothelial peroxisome proliferator-activated receptor gamma accelerates diet-induced atherogenesis in LDL receptor-null mice. Arterioscler Thromb Vasc Biol 32(1):65-73 |
| abstractText | OBJECTIVE: Peroxisome proliferator-activated receptor gamma (PPARgamma) is widely expressed in vessel walls, and it's activation by agonists showed beneficial effects in cardiovascular diseases. However, the role of endothelial cell (EC) PPARgamma in atherogenesis is not fully understood. METHODS AND RESULTS: To assess the contribution of endothelial-specific PPARgamma in atherosclerosis, EC-specific PPARgamma disruption and LDL receptor (LDLR) double-knockout (PPARgamma(DeltaEC)/LDLR(-/-)) mice were developed. When challenged with a high-cholesterol diet for 4 weeks, PPARgamma(DeltaEC)/LDLR(-/-) mice exhibited severe atherosclerotic lesions compared to either their littermate controls or macrophage-specific PPARgamma disruption and LDLR double knockout (PPARgamma(DeltaMPhi)/LDLR(-/-)) mice. Metabolic analysis showed severe dyslipidemia and significant increase in systolic blood pressure in the PPARgamma(DeltaEC)/LDLR(-/-) mice. Histological analysis and real-time quantitative PCR suggested an exacerbated inflammation in PPARgamma(DeltaEC)/LDLR(-/-) mice, as revealed by the increases of proinflammatory gene expression and macrophage infiltration in vivo and in vitro. Furthermore, in vivo endothelial permeability was also increased by endothelial PPARgamma disruption. Bone-marrow transplantation studies, which reconstituted hematopoietic PPARgamma, demonstrated that the accelerated atherogenesis was due to endothelial PPARgamma deficiency. CONCLUSIONS: Endothelial PPARgamma plays an important protective role in atherogenesis. |
