Adiponectin diminishes platelet aggregation and sCD40L release. Potential role in the metabolic syndrome

Abstract

(CD40L), is increased in the metabolic syndrome (MS) and released from platelets. We hypothesized that adiponectin modulates platelet function, and we sought to evaluate the association of adiponectin and sCD40L levels with platelet aggregation in MS and the effects of adiponectin on platelet aggregation and activation. Platelet aggregation and circulating adiponectin, sCD40L and P-selectin were determined in 30 controls and 30 patients with MS. Also, in vitro studies were performed in platelet-rich plasma from nine healthy volunteers. Adiponectin receptors were demonstrated by Western blotting and flow cytometry. ADP and epinephrine platelet aggregation was measured after preincubation with adiponectin. sCD40L and P-selectin secretion was measured in the supernatants by ELISA. Patients with MS had higher sCD40L and P-selectin than controls (5.96 Ϯ 0.50 vs. 4.28 Ϯ 0.41 ng/ml, P Ͻ 0.05, and 151 Ϯ 8 vs. 122 Ϯ 9 ng/ml, P Ͻ 0.05). By contrast, adiponectin was lower in patients with MS than in controls (5.25 Ϯ 0.30 vs. 7.35 Ϯ 0.34 g/ml, P Ͻ 0.001). Higher platelet aggregation was found in MS. Adiponectin inversely correlated with P-selectin (R ϭ Ϫ0.35, P ϭ 0.009), sCD40L (r ϭ Ϫ0.24, P ϭ 0.05) and epinephrine and collagen induced aggregation (r ϭ Ϫ0.80, P ϭ 0.005; r ϭ Ϫ0.70, P ϭ 0.011). Platelets express the receptors for adiponectin. Platelet aggregatory response to epinephrine and ADP significantly decreased following preincubation with adiponectin (96 Ϯ 4 vs. 23 Ϯ 3%, P Ͻ 0.001, and 102 Ϯ 9 vs. 85 Ϯ 9%, P ϭ 0.004). Adiponectin prevented platelet sCD40L release (1.63 Ϯ 0.15 vs. 2.04 Ϯ 0.20 ng/ml, P Ͻ 0.001). Enhanced platelet aggregation and activation markers are found in MS associated with low adiponectin concentrations. Novel evidence is provided demonstrating that adiponectin has antithrombotic properties, since it inhibits platelet aggregation and platelet activation. soluble CD40 ligand; platelets; platelet activation; P-selectin THE METABOLIC MYNDROME (MS) consists of the convergence of a variety of risk factors in the same individual and is characterized by a general proinflammatory and prothrombotic state that interacts synergistically, causing or accelerating the progression of atherosclerosis. There are different definitions to describe this syndrome. Currently, the more accepted definitions are those of the National Cholesterol Education Program -Third Adult Treatment Panel (NCEP ATP III) and the World Health Organization (WHO). In both, obesity, insulin resistance, dyslipidemia, and hypertension are considered to underlie the metabolic syndrome. Prothrombosis is not yet included in any definition of MS, but the International Diabetes Federation (IDF) consensus group identifies a prothrombotic state related to MS and advises investigating the predictive power of these extra criteria for cardiovascular risk or diabetes. In fact, several investigations demonstrate the association between a prothrombotic state and diabetes (23), obesity (20), and hypertension (17).Furthermore, recent studies demonstrate th...

Association between Risk Factors for Vascular Dementia and Adiponectin

“…Plasma adiponectin levels are inversely related to the platelet activation status of patients with cardiovascular risk factors [20]. Adiponectin suppresses platelet aggregation in hyperlipidemic rats by reversing the increase in inducible nitric oxide synthase expression while enhancing endothelial nitric oxide synthase activation [77, 78]. Current studies have reported the association between adiponectin and various diseases because adiponectin has multiple roles in glucose and lipid metabolisms and vascular system.…”

Adiponectin and Vulnerable Atherosclerotic Plaques

“…In cultured vascular smooth muscle cells, adiponectin suppressed vascular smooth muscle cell proliferation and migration via direct binding to platelet-derived growth factor-BB (23). Adiponectin also inhibits platelet aggregation and thrombus formation; however, the mechanism of action remains unclear (101,115,116). Macrophages add to the enlarging necrotic core when they succumb to necrotic and apoptotic cell death (117).…”

Expression of plasma membrane receptor genes during megakaryocyte development

“…We received donated human umbilical cord blood (UCB) after obtaining informed consent. UCB was processed by addition of 6% (wt/vol) Hetastarch (Hospira, Lake Forest, IL) to a final concentration of 1.2% (28), and gravity sedimentation over 60 min. The leukocyte-enriched supernatant was removed and centrifuged for 10 min at 300 g, and the leukocyte-poor supernatant was removed.…”