High blood pressure and the vascular damage it does—leading to cardiovascular disease—is
an enormous emotional and financial burden on patients with chronically elevated blood
pressure and their loved ones.
Connections Between Stress and the Vascular System
This research project focuses on how DNA damage and repairs occur in the endothelium,
the tissue encasing the blood vessels, heart and other organs in the vascular system.
We seek to introduce several novel strategies to lower blood pressure by reducing
inflammation in the tissue that makes up the endothelium, restoring its functional
integrity for vascular health.
There is a gap in our understanding of how chronic stress impacts the endothelium
to promote hypertension, or high blood pressure.
This research will provide new treatment targets for lowering blood pressure that
originates in the nervous system due to stress, leading to findings that can be used
in real-world clinical and healthcare contexts.
This approach to the research is a new paradigm that complements the current understanding
of vascular system inflammation. The molecules within the mitochondria, the powerhouse
of the cell, may act as immune regulators in response to stress or pathogens. They
may also be responsible for the initiation or manifestation of chronic inflammation
observed in patients with chronically high blood pressure.
Will blocking the formation of mitochondrial ROS (reactive oxygen species) with Mito-Q
(mitochondria-targeted ubiquinone) be an effective therapy to block the development
of endothelial dysfunction and lower blood presure in mice exposed to chronic unpredictable
Will inhibition of VDAC (voltage-dependent anion channel) oligomerization and gasdermin
pore formation lower blood pressure and improve endothelium function?
Will antibodies to IL-1(beta) (interleukin-1 beta) and IL-18 (interleukin-18) block
the negative effect of these cytokines on the endothelium?
Will the novel TRIM-Away technique, used to degrade caspase, provide critical evidence
that inflammasome activation is playing a major role in the development of endothelial
dysfunction in neurogenic hypertension induced by chronic, unpredictable stress?
Purpose: To study the activation of NLRP3 (nucleotide-binding domain, leucine-rich–containing
family, pyrin domain–containing-3) and AIM2 (absent in melanoma 2) inflammasomes to
uncover important triggers and endogenous modulators of hypertension
Hypothesis: In hypertension induced by chronic unpredictable stress, oxidative stress leads to
release of mitochondrial DNA (mtDNA) into the cytoplasm. This mtDNA activates inflammasomes
leading to endothelial dysfunction and blood pressure elevation.
Method: Integrate physiological, pharmacological, biochemical, biomechanical, molecular and
cellular techniques to better understand the pathological role of the endothelium
Vision: New therapeutic targets to lower pressure in neurogenic hypertension making the clinical/translational
significance of this research high
Additional research focus: Related sexual dysfunction in males and females
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.