Date of Award
Winter 12-2-2025
Embargo Period
12-2-2027
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Medicine
College
College of Graduate Studies
First Advisor
Amy D. Bradshaw
Second Advisor
Kristine Y. DeLeon-Pennell
Third Advisor
Jeffrey Jones
Fourth Advisor
Donald Menick
Fifth Advisor
R. Amanda C. LaRue
Sixth Advisor
Justin Van Beusecum
Abstract
Post-traumatic stress disorder (PTSD) is a disabling psychological disorder characterized by chronic symptoms of intrusiveness, avoidance, and hyperarousal after a traumatic event. Patients diagnosed with PTSD have a two-times higher risk of experiencing an adverse cardiac event like myocardial infarction or stroke compared to patients without PTSD even after adjustment for confounding factors like diabetes, hypertension, and depression. While there are multiple clinical observations addressing a correlation between PTSD and cardiovascular disease (CVD) outcomes, basic science studies investigating potential mechanisms for the connection between PTSD and CVD are few.
The goal of this study was to define a scoring method using a murine model of cued fear conditioning (inescapable foot shock, IFS) to distinguish the cardiovascular phenotype of a PTSD-like behavioral phenotype. Controls, non-responders (NR), and PTSD-like mice at 2 time points [4-weeks and 8-weeks post-IFS] were compared to evaluate left ventricular structure and function along with physiological changes associated with PTSD-like behavioral symptomology.
At 8-weeks post-IFS, both male and female PTSD-like mice demonstrated prolonged isovolumetric relaxation time, whereas females exhibited additional signs of diastolic impairment, including elevated E/e′ ratio, increased left atrial diameter, and reduced ejection fraction compared to controls. The elevated fibrotic genetic and protein expression observed in female PTSD-like mice is likely contributing to LV stiffening and impaired relaxation in female PTSD-like mice.
Sex-specific immune alterations were also observed. Resident cardiac macrophages increased in male PTSD-like mice at 4-weeks post-IFS and in both sexes by 8-weeks. In contrast, splenic neutrophils were elevated and circulating B- and CD8+ T-cells were reduced exclusively in female PTSD-like mice. Single-cell RNA sequencing of bone marrow revealed enhanced activation of PTSD-like neutrophils, suggesting a potential priming of neutrophils that may promote cardiac pathology.
Collectively, these findings identify possible interconnected immune and fibrotic mechanisms that may underlie PTSD-associated cardiac dysfunction in a sex-dependent manner. This study provides novel mechanistic insight into the cardiovascular consequences of PTSD and establishes a foundation for future investigations aimed at understanding and mitigating CVD risk in trauma-exposed populations.
Recommended Citation
Corker, Alexa M., "Mouse Model of Post-Traumatic Stress Disorder Demonstrates Negative Alterations of Cardiac Homeostasis" (2025). MUSC Theses and Dissertations. 1088.
https://medica-musc.researchcommons.org/theses/1088
Rights
Copyright is held by the author. All rights reserved.