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

Background
The proinflammatory and proatherogenic mediator CD40L is increased in the metabolic syndrome (MS) and released from platelets. We hypothesized that adiponectin modulates platelet function.

Objective
To evaluate the association of adiponectin and sCD40L levels with platelet aggregation in the MS and the effects of adiponectin on platelet aggregation and activation. Subjects/Methods: 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 9 healthy volunteers. Adiponectin receptors were demonstrated by western blotting. ADP- and epinephrine platelet aggregation was measured after preincubation with adiponectin. sCD40L and P-selectin secretion was measured in the supernatants by ELISA.

Results
Patients with MS had higher sCD40L and P-selectin than controls (5.96±0.50 vs 4.28±0.41ng/mL, p<0.05 and 151±8 vs 122±9ng/mL, p<0.05). By contrast, adiponectin was lower in patients with the MS than in controls (5.25±0.30 vs 7.35±0.34µg/mL, p<0.001). Higher platelet aggregation was found in the MS. Adiponectin inversely correlated with P-selectin (R:-0.35, p:0.009), sCD40L (R:-0.24, p:0.05) and epinephrine and collageninduced aggregation (r=-0.80, p=0.005 and r=-0.70, p=0.011).

Platelets express the receptors for adiponectin. Platelet aggregatory response to epinephrine and ADP significantly decreased following preincubation with adiponectin (96%±4 vs 23%±3, p<0.001 and 102±9 vs 85%±9, p=0.004). Adiponectin prevented platelet sCD40L release (1.63±0.15 vs 2.04±0.20ng/mL, p<0.001).

Conclusions
Enhanced platelet aggregation and activation markers are found in the metabolic syndrome associated to low adiponectin concentrations. Novel evidence is provided demonstrating that adiponectin has anti-thrombotic properties, since it inhibits platelet aggregation and platelet activation.

CITATION  Am J Physiol Endocrinol Metab. 2010 May;298(5):E1072-7