AIM To investigate the role of C1q tumor necrosis factor-related protein 9 (CTRP9) in abnormal activation of diabetic platelets and its possible receptor pathway using a diabetic animal model.
METHODS A total of 64 male C57BL/6J mice aged 6-8 weeks were randomly and equally divided into 2 groups and they were respectively given a normal diet or a high-fat diet for 12 weeks. Their body weight, blood glucose, platelet count, insulin level and serum CTRP9 level were measured, and their homeostasis model assessment-insulin resistance (HOMA-IR) level was calculated. Whole blood was collected after anesthesia to determine the changes of platelet aggregation effect in different intervention groups.
RESULTS Compared with the normal diet group, mice on the high-fat diet had increased body weight, blood glucose, insulin levels, HOMA-IR index, decreased CTRP9 levels, and increased maximum platelet aggregation rate and area under the aggregation curve. The addition of CTRP9 in an in vitro setting improved the abnormal platelet aggregation in both groups of mice. The inhibition of abnormal platelet aggregation by CTRP9 was inhibited by the addition of the N-cadherin inhibitor ADH-1. Compared with platelets from mice given no intervention, no significant differences were found in these indices in the samples with ADH-1 only. These effects were found in both mice on a high-fat diet and mice on a normal diet.
CONCLUSION In an in vitro environment, CTRP9 inhibits abnormal platelet activation in diabetic mice and the effect of CTRP9 is lost after inhibition of N-cadherin function. Thus it is inferred that N-cadherin may be the receptor for CTRP9 to inhibit abnormal platelet activation.
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