Do Platelet-Derived Microparticles Play a Role in Depression, Inflammation, and Acute Coronary Syndrome?

Abstract

Background Major depression is an independent predictor of increased mortality in patients presenting with acute coronary syndromes (ACS). There have been several mechanisms proposed to explain the link between depression and ischemic heart disease. Both abnormal platelet physiology and inflammation have been suggested as potential confounding variables. Objective We set out to examine platelet activation, inflammation, and levels of depression in hospitalized patients presenting with ACS. Methods We enrolled 28 patients with ACS and assessed levels of depression by PHQ-9. Platelet activation was assessed by the measurement of platelet microparticle levels and platelet aggregation to adenosine diphosphate and serotonin. Inflammatory markers were assessed by the measurement of TNF alpha, IL-6, and CRP. Results We found that ACS patients with moderate depressive symptoms who had higher TNF alpha, IL-6, and CRP levels had higher levels of platelet microparticles. We also found that ACS patients with PHQ-9 ≥ 10 had higher platelet aggregation to ADP. Conclusion Our results suggest that patients hospitalized for the treatment of an ACS who have moderate depression have increased platelet aggregation. These patients also have a positive association between elevated inflammatory markers and platelet activation, thus suggesting a pro-inflammatory component in ACS patients with depressive symptoms that may alter platelet function. These results are intriguing in that a potential pathway to explain the connection between depression, inflammation, and increased cardiovascular thrombosis might be found when both platelet activation and inflammation are measured.

Venous Thromboembolism Risk With Antidepressants: Driven by Disease or Drugs?

“…These facts could suggest that increased VTE risk may actually be related to the depression itself and not the treatment. This concept is supported by previous reports of depressive symptoms as a risk factor for recurrent VTE, likely through a prothrombotic platelet phenotype, possibly mediated by platelet‐derived microparticles …”

Platelet Response to Serotonin in Patients With Stable Coronary Heart Disease

“…Serotonin-Hydrochloride and adenosine diphosphate (ADP) were added to PRP to obtain 0.3, 3, 5, 15, and 30 μmolar serotonin and 0.5, 5, 10, 20 μmolar ADP concentrations respectively. The range of concentrations used is the same as a recent study conducted showing association of depression score and platelet aggregation in patients with ACS 6 . Unlike ADP, 5-HT, in vitro, is a very weak platelet agonist that causes reversible platelet aggregation and is considered a ‘helper agonist’ hence it is generally used in conjunction with a second agonist when measuring platelet aggregation 7 .…”

Brain changes associated with thromboxane receptor antagonist SQ 29,548 treatment in a mouse model

“…Multiple TP receptor subtypes have been reported and are appealing targets for therapeutic intervention of inflammation-related pathology. Given the extensive literature demonstrating a proinflammatory, hypercoagulable platelet activation state positively correlating with depression behavior in humans (Musselman et al, 1996;Berk and Plein, 2000;Lederbogen et al, 2004;Morel-Kopp et al, 2009;Aschbacher et al, 2009;Gehi et al, 2010;Williams, 2012;Canan et al, 2012;Moreno et al, 2013;Neubauer et al, 2013;Lopez-Vilchez et al, 2014;Huang et al, 2014;Williams et al, 2014) and the modest literature suggesting elevated prothrombotic TXA 2 levels in depressed patients (Lieb et al, 1983), we examined whether a TP receptor antagonist would modulate depression and anxiety behavior in mice. We tested whether a highly selective TP receptor antagonist, SQ 29,548, would attenuate depression-like behavior in mice observed in the forced swim and hanging tail suspension tests and attenuate anxiety in open field and elevated zero maze tests.…”