title: Exaggerated platelet reactivity to physiological agonists in war veterans with posttraumatic stress disorder.
abstract: An association between traumatic stress and cardiovascular disease (CVD) is supported by various epidemiological studies. Platelet activation and binding of activated platelets to leukocytes contributes to the pathophysiology of CVD. Evidence of hyperactive sympathetic nervous system, altered expression of platelet α(2)-adrenoreceptors (α(2)AR), and altered platelet adenylate cyclase activity in patients with posttraumatic stress disorder (PTSD) suggest that platelet reactivity in PTSD may be altered as well. We tested whether platelet reactivity to increasing doses of adenosine-diphosphate (ADP), epinephrine (EPI), or their combination differs between war veterans with PTSD (n=15) and healthy controls (n=12). For this purpose, citrated whole blood was incubated with increasing concentrations of ADP (0.1, 1, 10 μM), EPI alone (10 nM, 100 nM, 1000 nM), or EPI (10 nM, 100 nM, 1000 nM) in combination with 0.1 μM ADP. A subset of samples was also incubated with 10 μM yohimbine (YOH), α(2)AR antagonist, to distinguish receptor-specific effects. Platelet CD62P expression and formation of platelet-leukocyte aggregates (PLA) [platelet-monocyte (P-Mo), -lymphocyte (P-Ly), and -neutrophil (P-Ne) aggregates] were measured using three-color flow cytometry. Platelet reactivity was higher in war veterans with PTSD when compared to controls, as determined by greater CD62P expression and formation of PLA in response to ADP alone or in combination with EPI. Platelet reactivity also correlated with the severity of PTSD symptoms. Preliminary experiments with YOH indicate that stress-associated EPI elevations may contribute to platelet activation through a α(2)AR-dependent mechanism. The enhanced platelet reactivity observed in our study may be the underlying mechanism contributing to the development of CVD in PTSD patients.
authors.affiliation: University Hospital Dubrava, Department of Psychiatry, Referral Center for the Stress-Related Disorders, Zagreb, Croatia. avidovic@gmail.com
authors.forename: Anđelko
authors.initials: A
authors.lastname: Vidović
authors.forename: Mirjana
authors.initials: M
authors.lastname: Grubišić-Ilić
authors.forename: Dragica
authors.initials: D
authors.lastname: Kozarić-Kovačić
authors.forename: Katja
authors.initials: K
authors.lastname: Gotovac
authors.forename: Iva
authors.initials: I
authors.lastname: Rakoš
authors.forename: Alemka
authors.initials: A
authors.lastname: Markotić
authors.forename: Sabina
authors.initials: S
authors.lastname: Rabatić
authors.forename: Dragan
authors.initials: D
authors.lastname: Dekaris
authors.forename: Ante
authors.initials: A
authors.lastname: Sabioncello
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D000328:Adult; D001791:Blood Platelet Disorders / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology; D016022:Case-Control Studies; D017523:Croatia; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000187:drug effects* / Q000502:physiology; D013313:Stress Disorders, Post-Traumatic / Q000097:blood* / Q000150:complications / Q000453:epidemiology; D014728:Veterans / Q000523:psychology; D014857:Warfare; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D015016:Yohimbine; D000244:Adenosine Diphosphate; D004837:Epinephrine