Klotho reduction aggravates IS-induced platelet hyperactivation. (A) Serum Klotho levels in CKD mice after AST-120 treatment (n = 8). Data are mean ± SD. **P < .01 vs sham group; ^##P < .01 vs CKD group, ANOVA. (B) Serum Klotho levels in klotho^+/− mice (n = 8). Data are mean ± SD. **P < .01 vs WT group, Student t test. (C-J) WT and klotho^+/− mice were IP injected with IS (100 mg/kg per day) for 8 weeks. (C) Serum IS levels were measured in WT and klotho^+/− mice after IS treatment (n = 8). (D) Flow cytometric analysis of the concentration of PMPs in whole blood (n = 6). (E) Flow cytometric analysis of the percentage of platelet-monocyte aggregates in whole blood in vivo (n = 6). (F) Flow cytometric analysis of platelet-induced CD11b expression in platelet-associated monocytes (n = 6). (G) Quantification of the area of platelet adhesion for each group (n = 6). (H) The time for carotid artery occlusion by thrombus for each group (n = 6). (I) Flow cytometric analysis of ROS levels in platelets (n = 6). (J) Flow cytometric analysis of the expression of P-p38MAPK in platelets (n = 6). (C-J) Data are mean ± SD. *P < .05, **P < .01 vs WT group, Student t test.