Fig. 7.

ISIDE11 activates SIRT1 to protect against thrombosis and platelet activation associated with MTHFR deficiency. A In vivo settings of thrombosis model. B Representative western blot analysis of vessels obtained at the end of in vivo treatments. C Bleeding time evaluation in Mthfr heterozygous mice and relative control littermates treated as indicated. D Dose–response curves to acetylcholine (ACh) of phenylephrine-precontracted mesenteric arteries from Mthfr heterozygous mice and relative control littermates treated as indicated. E Blood flow velocity measurement in femoral artery of Mthfr heterozygous mice and relative control littermates treated as indicated. F Immunohistochemical analysis of the femoral artery lesion in Mthfr heterozygous mice and relative control littermates treated as indicated. Images were acquired using a Nikon DS-Ri1 camera with a 20X objective; scale bar, 25 μM. Right graph shows the semi-quantitation of lumen area expressed in percentage. G Aggregation of platelets isolated from WT, homo- and heterozygous MTHFR subjects incubated with ISIDE11. Statistical analysis was determined by 2-way ANOVA followed by Bonferroni’s post hoc test. *p < 0.05; **p < 0.001; ^#p < 0.05 vs ± plus ISIDE11; ^##p < 0.001 vs ± plus ISIDE11