Abstract 4143729: PTSD-Dependent Acceleration of Aortopathy

Post-traumatic stress disorder (PTSD) is associated with hypertension and increased heart rate, which are risk factors for cardiovascular disease including thoracic aortic aneurysms. A connection between stress and aortopathy has been suggested, yet mechanisms linking the two remain unknown. We hypothesize that PTSD-induced mechanical signals alter thoracic aortic wall homeostasis, which can predispose to aortopathy. C57BL/6 mice underwent traumatization consisting of inescapable foot shock, single prolonged stress, and single housing. PTSD phenotype was assessed through behavioral testing for the DSM-V PTSD criteria. Group-housed control mice did not undergo the traumatization but were subjected to behavioral testing. Z-scores for each behavioral test were generated and mice with z-scores above the 85% confidence interval on all criteria were considered to have a PTSD-like phenotype. This protocol yielded a PTSD phenotype in 30% of mice mimicking the human proportion of PTSD development following a traumatic experience. PTSD mice had significantly higher systolic blood pressures (PTSD (n=10), 149 ± 7mmHg; control (n=10), 123 ± 9mmHg, p<0.05) and lower plasma renin concentrations (PTSD (n=5), 52,233 ± 4,591pg/mL; control (n=5), 80,824 ± 10,797pg/mL, p<0.05) 4-weeks post-traumatization, suggesting a PTSD-induced renin-independent hypertension. Thoracic aortae were harvested 4-weeks post-traumatization and analyzed for changes in compliance by parallel-wire myography and alterations in aortic wall structure by histology. PTSD mice had enhanced thoracic aortic wall stiffness indicating increased extracellular matrix remodeling. Thoracic aortic aneurysms (TAAs) were induced surgically (periadventitial application of 0.5M CaCl 2 to the descending thoracic aorta) at 4-weeks post-traumatization. PTSD mice had significantly larger TAAs 4-weeks post-TAA induction demonstrating an acceleration of aortopathy (PTSD (n=5), 73.9 ± 13% increase from baseline diameter; control (n=5), 29.9 ± 6.9%, p <0.05). Our PTSD model recapitulated the human phenotype showing elevated systolic blood pressure. This hypertension is renin-independent potentially derived from alterations in neural circuits propagating a neurogenic hypertension. PTSD mice demonstrated extracellular matrix remodeling and acceleration of thoracic aortic aneurysm progression. Thus, PTSD can alter thoracic aortic wall homeostasis predisposing to or accelerating existing pathology.