Hepatocyte RXR alpha deletion in mice leads to inhibition of angiogenesis.

To investigate the effect of RXRalpha deficiency in liver on angiogenesis, hepatocyte RXRalpha-deficient and control wild-type mice were fed either standard or high-fat diet (HF) for 7 weeks. In the 6th week of feeding, Matrigel model of in vivo angiogenesis was applied. Matrigel plug infiltrating cells were then used for visualization of vessels (CD31 staining) as well as for gene expression analysis. HF diet appeared to decrease angiogenesis in hRXRalpha-deficient mice. Genes related to angiogenesis (Nos3, Kdr) were down-regulated, whereas genes connected with adipogenesis (Cebpb, Srebf1), apoptosis (Gzmb, Bcl2) and proinflammatory pathway (NfkappaB, Tnfalpha) were up-regulated by HF diet in hRXRalpha-deficient mice in the microarray study. Our results suggest that impaired fatty acid metabolism in liver (hRXRalpha-deficient mice) leads to impaired angiogenesis due to lipotoxicity and promotion of adipogenesis.