Platelet response to serotonin in patients with stable coronary heart disease

Abstract

Patients with heart disease and depression have an increased mortality rate. Both behavioral and biologic factors have been proposed as potential etiologic mechanisms. Given that the pathophysiology of depression is considered to involve disruption in brain serotonergic signaling, we investigated platelet response to serotonin stimulation in patients with stable coronary artery disease (CAD). We enrolled 92 patients with stable CAD. Platelet response to increasing concentrations of serotonin (5-HT), epinephrine-augmented 5-HT, and adenosine diphosphate (ADP) was measured by optical aggregation and flow cytometry. As concentrations of 5-HT and ADP increased, so did the activation and aggregation of the platelets. However, on addition of the highest concentration of 5-HT (30 μM), a significant decrease in platelet activation (p=0.005) was detected by flow cytometry. This contrasts the increase in platelet activation seen with the addition of the highest concentration of ADP. In conclusion, we found increased platelet activation and aggregation with increased concentrations of ADP; however, when platelets are stimulated with a high concentration of 5-HT (30 μM), there is decreased platelet activation. The data demonstrate unique patterns of platelet activation by 5-HT in patients with stable CAD. The cause of this phenomenon is unclear. Our study sheds light on the in vitro response of platelet function to serotonin in patients with stable CAD, which may further the mechanistic understanding of heart disease and depression.

FIGURE 1

Mean percent of platelet activation in response to increasing 5HT and ADP concentrations. 5HT = serotonin; ADP = adenosine diphosphate.

FIGURE 2

Mean percent of platelet aggregation in response to increasing concentrations of 5HT and ADP. Abbreviations as in Figure 1.

FIGURE 3

Serotonin pathway in platelets. 5-HT = serotonin; 5HT2AR = serotonin receptor type 2A; SERT = serotonin transporter; PLC = phospholipase C; DAG = diacyl glycerol; IP₃ = inositol 1,4,5-triphosphate; PKC = protein kinase C; Tgase = transglutaminase; VMAT = vesicular monoamine transporter 2; COAT = collagen and thrombin activated.