Endothelium-specific E1841K mutant hinders cAMP-mediated VWF release, prolongs bleeding time, and impairs thrombosis in mice. (A) Normalized levels of plasma VWF from cre-/E1841K^flox/flox (red), PF4-cre/E1841K^flox/+ (light green), PF4-cre/E1841K^flox/flox (dark green), Tie2-cre/E1841K^flox/+ (light blue), and Tie2-cre/E1841K^flox/flox (dark blue) (n = 14) mice before (B) and after epinephrine stimulation (E). (B) Bleeding times of cre-/E1841K^flox/flox (red), PF4-cre/E1841K^flox/+ (light green), PF4-cre/E1841K^flox/flox (dark green), Tie2-cre/E1841K^flox/+ (light blue), and Tie2-cre/E1841K^flox/flox (dark blue) (n = 16) mice after epinephrine stimulation (*P < .05; **P < .01; ***P < .001 vs cre-/E1841K^flox/flox mice). (C) VWF multimer distribution of basal mice plasma. (D) Ratios of high to low molecular weight of VWF multimers in C (NS > 0.05). (E) FeCl₃-induced thrombus formation in the mesenteric vessels of cre-/E1841K^flox/flox, PF4-cre/E1841K^flox/+, PF4-cre/E1841K^flox/flox, Tie2-cre/E1841K^flox/+, and Tie2-cre/E1841K^flox/flox (n = 8) mice. The thrombus is indicated with Rhodamine-labeled platelets and FITC-conjugated anti-VWF antibody. (F) The coverage of the area by thrombus in (E) at 15 minutes (*P < .05; ***P < .001).