Abstract
Platelet hyper-reactivity is a crucial cause of accelerated atherosclerosis increasing risk of thrombotic vascular events in diabetic patients. The mechanisms leading to abnormal platelet activity during diabetes are complex and not fully defined. The current study attempted to clarify the role of CTRP9, a novel adiponectin paralog, in enhanced platelet activity and determined whether CTRP9 may inhibit platelet activity. Adult male C57BL/6 J mice were randomized to receive high-fat diet (HFD) or normal diet (ND). 8 weeks after HFD, animals were sacrificed, and both plasma CTRP9 and platelet aggregation were determined. HFD-fed animals increased weight gain significantly, and became hyperglycemic and hyperinsulinemic 8 weeks post-HFD. Compared to ND animals, HFD animals exhibited significantly decreased plasma CTRP9 concentration and increased platelet response to ADP, evidenced by augmented aggregation amplitude, steeper aggregation slope, larger area under the curve, and shorter lag time (P < 0.01). A significant negative correlation between plasma CTRP9 concentration and platelet aggregation amplitude was observed. More importantly, in vitro pre-treatment with CTRP9 significantly inhibited ADP-stimulated platelet activation in platelet samples from both ND and HFD animals. Taken together, our results suggest reduced plasma CTRP9 concentration during diabetes plays a causative role in platelet hyper-activity, contributing to platelet-induced cardiovascular damage during this pathologic condition. Enhancing CTRP9 production and/or exogenous supplementation of CTRP9 may protect against diabetic cardiovascular injury via inhibition of abnormal platelet activity.
Highlights
Anti-platelet treatment, such as acetylsalicylic acid and aspirin, reduces cardiovascular morbidity and mortality [1]
Plasma CTRP9 levels were significantly reduced in high-fat diet (HFD) induced type‐2 diabetic mice To confirm establishment of type 2 diabetes by HFD, body weight, plasma glucose, and insulin concentration were determined
Previous studies have reported an association between platelet activation and the degree of insulin resistance reflected by Homeostatic Model AssessmentInsulin Resistance (HOMA-IR) [23]
Summary
Anti-platelet treatment, such as acetylsalicylic acid and aspirin, reduces cardiovascular morbidity and mortality [1]. It is well known type 2 diabetic patients are at very high cardiovascular risk [2], and should thereby potentially benefit significantly from anti-platelet treatment. Concomitant type 2 diabetes increases the risk of high on-aspirin platelet reactivity (HPR), defined as inadequate inhibition. Present in plasma at concentrations up to 30 μg/ml, adiponectin is markedly down-regulated in association with obesitylinked diseases such as coronary artery disease and type 2 diabetes [7]. Clinical observations have revealed that plasma total adiponectin concentrations are inversely correlated with myocardial infarction risk [8, 9]. Adiponectin knockout mice have been generated and studied by many groups
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