The leading cause of death in industrialized countries, cardiovascular diseases (CVDs) are responsible for 40 percent of all deaths in the U.S., more than all forms of cancer combined. Many CVDs involve arteriosclerosis, or hardening of the arteries due to structural changes in blood vessel walls. To better understand the underlying physics of arterial stiffness—and ultimately, CVDs, Assistant Professor Katherine Yanhang Zhang (ME) aims to pinpoint the mechanisms that control structural and functional changes in blood vessel walls.
Now funded by a $1.15 million, four-year grant from the National Institutes of Health, Zhang plans to develop and validate a biomechanical model of the vascular extracellular matrix, specialized proteins that provide structural support to blood vessels and the development of cells. Coupling molecular-level structural protein mechanics to tissue-level behavior, this multi-scale model could enable researchers and clinicians to probe basic mechanisms behind CVDs and other vascular diseases, and ultimately design new therapies.
“Integrating molecular-to-tissue level information will provide a powerful tool to examine mechanical changes in the blood vessels due to these diseases, which will complement many existing biological findings in vascular remodeling,” said Zhang, who runs the Multi-Scale Tissue Biomechanics Laboratory. “We eventually hope to combine our biomechanical model with animal studies to understand vascular remodeling in CVDs.”
Zhang’s research focuses on the vascular extracellular matrix (ECM), which is essential to accommodate structural changes that occur during physiological functions, and acts as a cellular microenvironment that regulates cell growth and activity. Her group, which since 2006 has established modeling and experimental capabilities for studying ECM mechanics, aims to learn how specific mechanical properties of vascular systems’ ECM microenvironments contribute to events that may alter their shape and function—and possibly lead to arteriosclerosis.
“Our research seeks to establish a foundation to investigate the role of microstructural components in vascular remodeling,” said Zhang. “We envision this as a first step toward advancing the understanding of the relationship between fundamental arterial biomechanical changes and the development of CVDs.”
Her long term research goal is to enable patient-specific clinical studies using a combination of the multi-scale model and three-dimensional vascular anatomy imaging capabilities. “This should be useful in following disease progression, especially regarding the initiation and effects of arterial remodeling in CVDs,” she explained.
The proposed multi-scale model holds great potential for incorporating quantitative information from future advances in vascular biology, medical imaging and biomechanics—data that could enable researchers to predict patient-specific outcomes of alternate therapeutic interventions.