Advisor(s)

Jennifer Pollock

Committee Member(s)

André Ballesteros-Tato
Beatriz León-Ruiz
David Pollock
Michael Ryan
Subhashini Bolisetty

Document Type

Dissertation

Date of Award

1-27-2026

Degree Name

Doctor of Philosophy (PhD)

School

Joint Health Sciences (Interdisciplinary)

Department

Cellular and Molecular Physiology

Abstract

The term Early Life Stress (ELS) encompasses traumatic events occurring before the age of 18 such as physical abuse, verbal abuse, household dysfunctions, sexual abuse, childhood neglect, child maltreatment, and adverse childhood experiences. The traumatic psychological and physical experiences in early life are widely known to cause enduring effects on mental and physical health in adulthood. Of note, individuals with ELS have adverse health outcomes earlier in adulthood and with more severity such as in the case of Systemic Lupus Erythematous (SLE), an autoimmune disease. The risk for autoimmunity and cardiovascular disease (CVD) increases with ELS exposure and CVD is the predominant cause for early mortality in SLE patients. There is little known regarding the specific mechanisms that ELS induces in the vasculature and immune system to incur these risks and how early these changes may occur. This thesis addresses the gap in knowledge of why coexistence with ELS is associated with higher prevalence of CVD in the general population and in those who develop SLE. In the case of SLE— despite reports linking worsened disease activity in patients with ELS—there have been no studies in preclinical rodent models of SLE in conjunction with ELS. This project is designed with three aims. First, we collected blood pressure and hemodynamic outputs in human adolescents with or without ELS to understand what early changes occur after stress in childhood. Then, using mouse models, we explored the mechanism of vascular dysfunction in ELS by determining if macrophages, specifically through CSF-1, mediate ELS-driven aortic disruptions. Finally, additional mouse studies addressed if ELS mediates enhanced development of aortic disease in SLE through immune activation. Advances in the ELS field are essential to developing relevant and accessible intervention and prevention strategies for patients. This thesis identifies altered immune pathways following ELS, both in the presence and absence of comorbidity (e.g., SLE), and links these changes to measurable cardiovascular (CV) outcomes. The findings provide further insight into how ELS contributes to long-term CV risk and the tragic health consequences faced by individuals exposed to ELS during childhood.

Keywords

adverse childhood expereinces;aorta;childhood abuse;early life stress;macrophage;vascular

ProQuest Publication Number

32242292

ISBN

9798273387713

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