engleski

Cardiovascular disease-related inflammatory markers in prisoners of war

There is growing evidence that individuals with posttraumatic stress disorder (PTSD) are at higher risk of developing coronary heart disease. PTSD can be regarded as a prolonged stress reaction with associated neuroendocrine alterations which could contribute to initia-tion and development of atherosclerosis, thereby leading to cardiovascular disease (CVD). Studies have shown that PTSD is linked with the chronic low-grade inflammation which could be associated with systemic vascular inflammation and atherogenesis. In line with these notions, we have measured seven inflammatory markers involved in pathogenesis of atherosclerosis in detainees that were imprisoned in war camps during the war in Croatia. Two of these markers are primarily related to platelet activation (sCD40L, sP-selectin) while MCP-1 and IL-8 represent chemokines responsible for recruitment of inflammatory cells to vessel walls. sVCAM-1 is a member of adhesion molecules responsible for firm adhesion of the cells to the vessel walls and tPA reflects fibrinolytic activity. IL-6 is one of the major pro-inflammatory cytokines that plays a significant role in virtually all stages of the inflammatory response (for details about these markers and recent findings in human chronic stress states please refer to the box at the bottom “ Inflammatory markers” ). A total of 31 male detainees imprisoned in war camps during 1991 and 1992 (detention lasting from 6 to 332 days) were examined in 2007 as a part of special medical program led by Croatian Government. All the participants underwent thorough clinical examination in-cluding psychiatric examination and psychometric testing. All the relevant demographic data were recorded and every participant was examined (including laboratory testing) for the presence of traditional CVD risk factors (smoking, hypertension, hyperlipdaemia, obesity, diabetes). For this purpose body mass index, blood preassure, blood glucose, and serum lipids levels were determined. Citrated whole blood was collected by venipuncture followed by immediate plasma separation. Plasma concentrations of soluble CD40 ligand (sCD40L), soluble P-selectin, monocyte chemoattractant protein 1 (MCP-1), tissue-type plasminogen activator (t-PA), vascular cell adhesion molecule 1 (VCAM-1), interleukin-6 (IL-6), and interleukin-8 (IL-8) were determined by FlowCytomix Human Cardiovascular 7plex kit (Bender MedSystems, Vienna, Austria), bead array system for simultaneous determination of multiple analytes by flow cytometry. Seventeen participants were diagnosed with PTSD according to ICD-10 and DSM-IV crite-ria. Analysis of association of PTSD diagnosis and PTSD related symptoms with measured inflammatory markers will be presented and discussed. Life-style related variables, as well as other identified CVD risk factors will be taken into account in all analyses. Plasma concentrations of sCD40L tends to be higher, while concentrations of tPA tends to be lower in PTSD subjects indicating higher platelet activation and decreased fibrinolytic activity. Possibly decreased tPA levels may be important because the recent evidence sug-gests that the tPA-plasminogen system is important for neuronal plasticity and survival through the BDNF/proBDNF pathway. Negative correlation of the PTSD-related symptoms with the plasma concentration of che-mokines (IL-8, MCP-1) suggests possible involvement of psychological factors in regulation of chemotaxis during inflammation. Although not all of the subjects met criteria for PTSD, a high levels of PTSD related symp-toms were present in all participants. Participants with PTSD had more pronounced symp-toms of depression including 3 participants with major depression. Inclusion of the healthy control group, without war camp experience and major depression, is needed to test the specific influence of war camp-related experience on measured markers. This would also possibly explain our finding of generally high levels of sVCAM in all participants (much higher than reference values or those found in other studies). In this preliminary study we have identified all the problems related to the method used for determination of inflammatory markers (sample collection, processing and storing, flow cytometry). We have also roughly identified expected changes in measured markers to de-termine sample size for future analysis. Final study will include 70 participants with the inclusion of the healthy control group. The analysis will be based on regression model identifying predictors associated with CVD inflammatory markers in prisoners of war.

PTSP; kemokini; citokini; upala

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