Patient populations with higher prevalence of autoimmune disease—like women and those
of the female sex, veterans and those suffering from trauma and Black and African
American communities—are at higher risk for cardiovascular disease.
Connections Between High Blood Pressure and the Immune System
This project studies the contributions of the immune system and, specifically, the
kidneys to high blood pressure induced by stress.
We are particularly interested in this research for populations where autoimmune disease
is statistically high and where autoimmune diseases are population-specific, such
as those of the female sex, veterans and those suffering from trauma and Black and
African American communities.
While it is known that chronic stress, trauma exposure and post-traumatic stress disorder
can promote cardiovascular and autoimmune disease, the mechanisms by which stress
impacts the kidneys to drive this risk are not clear. This research project focuses
on identifying that connection with a focus on the patient populations most impacted
by chronic stress.
Understanding the link between how the kidneys and immune system are impacted by stress
helps to fill an important knowledge gap in cardiovascular disease research.
This study takes an innovative approach involving the function of the mitochondria
and the impacts of inflammatory hormones released on blood pressure and kidney function.
We are using state-of-the-art techniques on the physiology, pharmacology and molecular
levels to test our hypothesis of the impacts of stress on the kidneys and immune system.
Our findings will further set the stage to probe the role and impact of genetics as
it relates to stress and the immune system.
Does CUS (chronic unpredictable stress) superimposed on SLE (systemic lupus erythematosus)
accelerate autoimmunity and exacerbate hypertension and renal disease?
Does the NLRP3 (nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3)
inflammasome mechanistically contribute to CUS-induced renal disease and hypertension
Do NETs (neuroendocrine tumors) mechanistically promote renal dysfunction and hypertension
Are reactive oxygen species mediators of an innate immune feed forward system promoting hypertension
when CUS is superimposed on SLE?
Purpose: To address a critical knowledge gap about the mechanisms by which chronic stress and
innate immunity interact to promote renal disease and hypertension
Hypothesis:Superimposing chronic unpredictable stress (CUS) on systemic autoimmunity impairs renal
mitochondrial function leading to activation of the NLRP3 (nucleotide-binding domain,
leucine-rich–containing family, pyrin domain–containing-3) inflammasome and the downstream formation
of neutrophil extracellular traps (NETs) to drive renal reactive oxygen species production
Goal: To directly examine the intersection of stress, innate immune system function, and
autoimmune associated renal disease and hypertension
Vision: While it is known that chronic stress, trauma exposure, and PTSD can promote hypertension
and autoimmunity, the mechanisms by which stress impacts the kidney to drive this risk
are not clear. This project is highly significant because it will begin to fill this
important knowledge gap. Importantly, the model used in this project closely mimics
human SLE, and studies using this model have been translated directly to humans, making
the clinical/translational significance high.
While this research improves the lives of anyone who has cardiovascular disease or
knows someone with cardiovascular disease in South Carolina—a high percentage of the
population—certain groups will benefit greatly from this focus area and the institute's
work at large.
Women and the Female Population
This research will improve the lives of anyone who has cardiovascular disease or knows
someone with cardiovascular disease in South Carolina. However, certain groups will
greatly benefit from our focus area and the institute's work at large.
Black and African American Communities
High blood pressure disproportionately affects African American communities. This
community experiences high heart failure rates despite health providers meeting standard
of care guidelines. The institute will shed light on how body responses to everyday
situations increase the likelihood of cardiovascular disease in these populations.
Veterans and Those Suffering from PTSD or Trauma
Exposure to trauma affects the body in significant ways, especially the heart and
vascular system. Veterans are at higher risk of having a new onset of heart disease
compared with non-veterans. This research contributes directly to improving the lives
of veterans and those with trauma or PTSD, while adding to the overall knowledge base
of care for veterans.