Depression and Cardiovascular Disease: The Viewpoint of Platelets

Figures

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  Figure 3. Increased oxidative stress that occurs during major depressive disorders (MDD), can activate platelets. Depressed patients are characterized by an imbalance in redox system with increased pro-oxidant enzyme activity not counterbalanced by anti-oxidant enzyme [251,252,253,276,278,279]. This imbalance promotes an excessive production of ROS and an increase in F2 isoprostanes circulating levels. Extracellular ROS is then able to activate platelets increasing GPIIb/IIIa receptor affinity, and inducing GPIα and GPVI receptors shedding with consequent activation of downstream pathways [282,283]. In the same time, the activation of platelets due to pro-oxidant environment favors intra-platelets production of ROS. Intra-platelets ROS support platelet activation promoting α-granule exocytosis, increasing the sensitivity of platelet receptors, acting as second messenger in thrombin- or collagen-activated platelets, inducing calcium mobilization, upregulating CD40L surface expression and release and generating isoprostanes, including 8-iso-PGF2α [activating AA metabolism] [290,291,292,293,294]. PGF2α can in turn activates TX receptor beyond supporting platelet activation [295,296,297].…

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  Figure 1. Platelets of depressed patients show hyper-reactivity. Patients with depression, show hyper-reactive platelets. Indeed, platelets of depressed patients display a greater exposure of anionic phosphatidylserine determinants, an increased activation of Glycoprotein IIb/IIIa, a higher expression of P-selectin and Glycoprotein Ib, an increased expression and sensitivity of 5HT2 receptor, an enhanced activity of SERT and an enhanced aggregation and sensitivity in response to collagen thrombin, and serotonin. Platelet hyper-reactivity is also confirmed by a greater platelet granules secretion. GP: Glycoprotein; vWF: von Willebrand Factor; 5-HT: 5-Hydroxytriptamine; 5-HT2: 5-HT receptor; SERT: plasma membrane serotonin transporter. ↑: increased compared to control.

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  Figure 2. The controversial role of BDNF on platelet function. Depressed patients are characterized by the reduction of BDNF levels in the brain, that is well reflected by its decreased plasma and serum levels [221,222,223]. Remarkably, platelet BDNF content is reduced in depressed patients [224], but antidepressant treatment is able to restore their levels [224], indicating that a pre-activated state may promote platelet emptying of their BDNF reservoir. Platelets, when activated, can release BDNF [154,215,217,218], and extracellular BDNF can bind a specific site on platelets surface with subsequent internalization [215]. However, there are no information about its possible effect on platelets. BDNF: Brain-derived Neurotrophic Factor.