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Institute for Cardiovascular Disease Research

Project 1: Vascular System and Stress

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.

Project Significance

  • 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.

Research Innovation 

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.

Research Questions

  1. 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 stress?

  2. Will inhibition of VDAC (voltage-dependent anion channel) oligomerization and gasdermin pore formation lower blood pressure and improve endothelium function?

  3. Will antibodies to IL-1(beta) (interleukin-1 beta) and IL-18 (interleukin-18) block the negative effect of these cytokines on the endothelium?

  4. 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 in hypertension

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


SC Impact

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.


Notable Awards, Outcomes and Practical Uses for this Research 

  • Air Force Partnership: Equipment grant for polygraph application of research by biomedical engineers at USC
  • American Physiology Summit Presentation: Collaborative, interdisciplinary presentation, April 2023
  • Multi-PI grant in partnership with Vanderbilt University
  • 8-Day School for Cardiovascular Disease at Loyola University: Sponsored by the American Journal of Hypertension

Institute for Cardiovascular Disease Research

    Challenge the conventional. Create the exceptional. No Limits.