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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 -/- ApoB 100/100 mice were generated by crossbreeding low-density lipoprotein receptor-deficient mice that synthesize only apolipoprotein B100 (LDLR -/- ApoB 100/100 ) 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 -/- ApoB 100/100 mice, as assessed non-invasively using ultrasound biomicroscopy prior and after treatment, and histologically after termination. Treatment had no impact on plaque composition (i.e. muscle, collagen, macrophages). The reduced plaque area could not be explained by effects of A-285222 on plasma glucose, insulin or lipids. Inhibition of nuclear factor of activated T-cells was associated with increased expression of atheroprotective NOX4 and of the anti-oxidant enzyme catalase in aortic vascular smooth muscle cells., Conclusion: Targeting the nuclear factor of activated T-cells signalling pathway may be an attractive approach for the treatment of diabetic macrovascular complications.

Baccharis trimera (Less.) DC is a South American plant that in folk medicine is considered to produce reduction in blood pressure. One aspect of this putative effect is the vasorelaxation. The aim of this work was to evaluate the ability of a B. trimera extract to relax rat aortic rings precontracted with noradrenaline. As the infusion is the usual way of intake of this plant, an infusion of B. trimera was prepared using 100 g of the plant (leaves) boiled in water, frozen and lyophilized. Working solutions were prepared using different concentrations of the dried extract diluted in Krebs Henseleit solution. It was proved that the infusion relaxed the aortic rings in a dose dependent manner 100 minutes after adding the exract to the bath. Considering as 100% the maximum contraction achieved with noradrenaline, a relaxation of 101.1 ± 2.3% was observed with the highest dose of the infusion used in these experiments (0.32 mg/mL). While in control rings relaxation was 12.9 ± 2.4%. In aortic rings denuded from endothelium the percentage of vasoralaxation did not show statistically significant differences when compared to intact rings. These data support the hypothesis of a vasorelaxant effect of this plant and constitutes the first approach to the scientific basis of a potential antihypertensive effect.