LAUSR

Objective: Post-traumatic stress disorder (PTSD) in patients is associated with hypertension, increased heart rate, and elevated plasma proinflammatory cytokines, which also are risk factors for the development of cardiovascular conditions, such as thoracic aortic aneurysm (TAA). Although the association between stress and aortic pathology has been suggested, the exact mechanism linking the two is unknown. Our hypothesis is that PTSD-induced changes in mechanical and inflammatory signaling alter thoracic aortic wall homeostasis, which can predispose to aortic disease. Methods: Adult male and female C57BL/6 mice (n=7) underwent PTSD induction consisting of inescapable foot shock (five x 1 sec, 1 mA foot shocks over 6 min paired with a 20 sec 80 db tone (conditioned stimulus)) followed by single prolonged stress events. Mice were subjected to behavioral testing at 4-week intervals over a 16-week paradigm to determine their PTSD-like phenotype. The behavioral tests were chosen to assess for each of the human criteria of PTSD based on the DSM-5. A composite t-score was generated for each mouse derived from their mean individual z-score for each parameter, of each behavioral test. Mice with a composite t-score above 1.96 were considered to have a PTSD-like phenotype. Blood pressure was measured (CODA, tail-cuff) at baseline and at 4-week intervals. At terminal study, thoracic aortic diameter was measured by digital microscopy. Plasma was collected to measure circulating cytokines and aortic tissue was harvested for biochemistry and histology. Aortic structure was examined for changes in elastic lamellae, collagen deposition, and cellular content. Control mice (n=8) underwent the same procedures except for PTSD induction. Results: Our protocol generated a PTSD-like phenotype in 71% (5 of 7) of the mice. PTSD mice had significantly higher systolic blood pressures following a conditioned stimulus (PTSD (n=5), 153 ± 8mmHg; control (n=8), 129 ± 7mmHg, p<0.05). PTSD mice also had increased plasma proinflammatory cytokines (IL1-α, IL-3, IL-5, IL-7, IL-9, all p<0.05), enhanced extracellular matrix remodeling (ECM), and larger aortic diameters than control mice (PTSD (n=5), 712.9 ± 97.6μm; control (n=8), 584.2 ± 102.7μm, p <0.05). Conclusion: Our PTSD-like mouse model recapitulated the human phenotype showing elevated systolic blood pressure and increased circulating proinflammatory cytokines. Increase thoracic aortic diameter and changes in the ECM suggest that PTSD can alter structural homeostasis in the aortic wall, predisposing the thoracic aorta to development of further pathology. Future studies will examine PTSD effects on TAA progression in a mouse model. NIH-NCATS TL1 TR00145-08 & UL1TR001450-08 (HH) and VA Merit Award I01-BX000904-08A1 (JAJ) 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.