Vasculopathy and changes in plasma ADAMTS13 and VWF profiles in FH W1206R mutant mice. (A) Endothelium-dependent and independent relaxation of small mesenteric arteries was impaired in FH^R/R mice. The endothelium-dependent nature of the phenotype was established by the use of inhibitors of nitric oxide synthase (L-NAME), COX (INDO), and K_Ca (TEA). An endothelium-independent component of the phenotype was indicated by the use of SNP, which acts directly on vascular smooth muscle cells. Three vessel segments per mouse were analyzed (n = 3 mice). (B) ADAMTS13 activity and plasma VWF levels were significantly higher in FH^R/R mice than in FH^W/W or FH^R/R mice (n = 7 per group for ADAMTS13; n = 3 per group for VWF). (C) Western blot of plasma VWF shows that FH^R/R mice had higher levels of total VWF (n = 5; each lane represents 1 mouse) and more abundant lower-molecular-weight (MW) multimers. (D) The ratio of high- to low-molecular-weight VWF multimers, as defined in panel C and quantitated using ImageJ software, was significantly lower in FH^R/R mice. Data are from 8-week-old FH^W/W, FH^W/R, and FH^R/R mice. Data in panels B,D represent mean ± SD of results from all mice. *P < .05; **P < .01; ***P < .001 (one-way ANOVA and Student t test). AA, arachidonic acid; eNOS, endothelial nitric oxide synthase; MW, molecular weight; NO, nitric oxide; PGI₂, prostaglandin I₂.