Endothelial PPARγ modulates atherosclerosis by regulating endothelial activation and prostacyclin levels

ABSTRACT: Systemic activation of the nuclear receptor peroxisome proliferator activated receptor gamma (PPARγ), a key regulator of glucose and lipid homeostasis, has been shown to result in amelioration of atherosclerosis in animal and human studies. However, the pathways and tissues through which this occurs remain unclear. As endothelium is involved in the development of atherosclerosis and expresses PPARγ, we propose a role for endothelial PPARγ in atherogenesis. Using a mouse model of endothelial PPARγ deficiency, we found that these mice developed more severe atherosclerosis in response to dietary challenges and exhibited increased levels of serum and aortic adhesion molecules. Gene expression analyses of primary endothelial cells isolated from mouse hearts revealed that the endothelial cells lacking PPARγ on chow diet displayed an expression profile similar to wild-type endothelial cells on an atherogenic diet, suggesting that PPARγ knockout endothelial cells are already activated prior to diet-induced hypercholesterolemia. In particular, the expression of cytokines, as well as prostacyclin synthases, was altered in PPARγ-deficient endothelial cells. Thus, we propose a mechanism by which endothelial PPARγ exerts an athero-protective role via transcriptional activation of cytokine and prostacyclin synthesis genes during the initiation phase of atherogenesis.

ORGANISM(S): Mus musculus

PROVIDER: GSE42419 | GEO | 2026/02/26

REPOSITORIES: GEO