In vivo inhibition of nuclear factor of activated T-cells leads to atherosclerotic plaque regression in IGF-II/LDLR –/– ApoB 100/100 mice

Aims:Despite vast clinical experience linking diabetes and atherosclerosis, the molecular mechanisms leading to accelerated vascular damage are still unclear. Here, we investigated the effects of nuclear factor of activated T-cells inhibition on plaque burden in a novel mouse model of type 2 diabetes that better replicates human disease.Methods & Results:IGF-II/LDLR–/–ApoB100/100 mice were generated by crossbreeding low-density lipoprotein receptor–deficient mice that synthesize only apolipoprotein B100 (LDLR–/–ApoB100/100) with transgenic mice overexpressing insulin-like growth factor-II in pancreatic β cells. Mice have mild hyperglycaemia and hyperinsulinaemia and develop complex atherosclerotic lesions. In vivo treatment with the nuclear factor of activated T-cells blocker A-285222 for 4 weeks reduced atherosclerotic plaque area and degree of stenosis in the brachiocephalic artery of IGF-II/LDLR–/–ApoB100/100 mice, as assessed non-invasively using ultrasound biomicroscopy prior and after treatment, and...