Texas Tech University researcher Dr. Zhongkui Hong has received a $594,288 grant from the National Heart, Lung, and Blood Institute, part of the National Institutes of Health, to investigate how interactions between cells and their surroundings contribute to atherosclerosis. The research could help identify new approaches to preventing or slowing the disease.
Hong, an associate professor in the Department of Mechanical and Aerospace Engineering in the Edward E. Whitacre Jr. College of Engineering, will lead the 3-year project, “Modulation of YAP/TAZ Signaling for the Prevention and Therapy of Cardiovascular Disease.”
Atherosclerosis develops as cholesterol-rich material, cells and other substances accumulate within artery walls to form plaques. These plaques can narrow arteries and restrict blood flow. If a plaque ruptures, it can trigger a blood clot that causes a heart attack or stroke.
Hong’s team is studying vascular smooth muscle cells, which normally occupy the middle layer of artery walls and help regulate vessel diameter and blood flow. During atherosclerosis, these cells can change their behavior and move into the artery’s inner layer, where they contribute to plaque development. Some also help form a protective covering that makes plaques less likely to rupture. These differing roles make it important to understand how the cells’ surroundings influence their behavior.
“We are taking a biomechanical approach to improving cardiovascular health,” Hong said.
The project focuses on how these cells attach to and respond to the extracellular matrix, the supporting network of proteins and other molecules around them. Matrix proteins such as collagen, elastin and fibronectin have distinct roles in supporting artery walls and interacting with cells. Changes in the matrix’s stiffness and protein composition can influence a cell’s internal structure, how it attaches to the matrix and how it moves.
Cells convert physical cues from their surroundings into biochemical signals through a process called mechanotransduction. Hong’s team is investigating YAP and TAZ, two proteins that help translate these cues into changes in gene activity. The researchers hypothesize that changes in matrix stiffness and composition alter YAP/TAZ signaling, disrupting how smooth muscle cells attach to different matrix proteins and contributing to abnormal migration.
Preliminary laboratory studies suggest that inhibiting YAP/TAZ signaling has different effects on molecular pathways associated with attachment to different matrix proteins. These findings provide a basis for testing how changes in signaling affect cell attachment and movement.
Through studies of cells and mouse models of atherosclerosis, the team will examine whether inhibiting YAP/TAZ signaling can rebalance cell attachment to matrix proteins and limit abnormal migration. The researchers will also test whether this approach reduces plaque formation or slows the progression of existing plaques, establishing whether changes in cell behavior translate into a benefit in these models.
By connecting the physical environment of artery cells with the molecular signals that guide their behavior, the project aims to reveal potential targets for future cardiovascular therapies. This research is being conducted in cells and animal models, and any benefit for patients will require further study.
The project will also provide undergraduate students with hands-on research experience at the intersection of engineering and biology and support the development of coursework in biomechanics and mechanobiology at Texas Tech.