PTSD induced inflammation negatively impacts cardiac homeostasis

Abstract

Multiple studies indicate that post-traumatic stress disorder (PTSD) is a risk factor for cardiovascular disease (CVD), however the mechanisms behind this correlation is unknown. We hypothesize that PTSD stimulates recruitment of monocyte-derived macrophages to the heart, resulting in increased cardiac fibrosis and resetting cardiac homeostasis. To induce experimental PTSD, male C57BL/6 mice were given 5 different foot-shocks (IFS; 1.0 mA, 1 sec duration) in 6 min. Before each shock, a tone was played to act as the PTSD-associated trigger. Control mice were also placed in the IFS chambers for 6 min but did not receive foot shocks. Behavioral testing was performed to characterize mice into non-responders (NR; IFS mice that do not demonstrate PTSD-like behavioral characteristics) and PTSD-like mice. Terminal timepoints selected were 4-weeks (4.6±0.7 months old) and 13-weeks (8.2±0.0 months old) post-IFS. Doppler echocardiography was collected at the 4-week time point. Histological and immunoblot assessments were collected at 13-weeks post-IFS to determine chronic alterations in cardiac homeostasis. Doppler measurements revealed that 4-weeks post-IFS, PTSD-like mice had decreased aortic ejection time (p<0.05) and trended toward increased isovolumetric relaxation (p=0.080) and contraction (p=0.088) time compared to controls. Interestingly at 13-weeks post-IFS, cardiomyocyte size was also elevated in PTSD-like mice compared to controls (p<0.05), suggesting the functional changes observed at 4-weeks reflect elevations in myocardial stress. A decrease in spleen weight at 4- (p<0.05) but not at 13-weeks (p=0.30) post-IFS indicate potential recruitment of immune cells acutely in PTSD-like mice. In line with spleen weights, at 4- and 13-weeks post-IFS, macrophage staining showed elevated levels in the LV of PTSD-like mice but not NR compared to controls (p<0.05 for all). In addition, matrix metalloproteinase (MMP)-9 protein levels were increased in the LV of PTSD-like mice compared to controls 13-weeks post-IFS (p<0.05). Collagen volume fraction was elevated at 13-weeks post-IFS in PTSD-like and NR mice compared to controls (p<0.05 for all). Our data indicates PTSD-induced cardiac stress is leading to macrophage recruitment and cardiac fibrosis which likely over time will lead to deterioration of myocardial function. This work was supported by the National Institutes of Health T32GM123055; the American Heart Association Innovator Project IPA35260039; the Biomedical Laboratory Research and Development Service of the Veterans Affairs Office of Research and Development Award IK2BX003922; and South Carolina Translational Research Center UL1TR001450 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.