Unhealthy blood vessels and endothelium can lead to serious health risks like hypertension and cardiovascular disease.
In her lab at Versiti Blood Research Institute, Investigator Magdalena Chrzanowska, PhD, FAHA, is attempting to answer one not-so-basic question: “We’re trying to understand exactly how human bodies work,” she said. As a basic researcher, her laboratory focuses on using disease models to help answer questions related to the human body. “We want to understand exactly how things work, and we do that using cells,” she said.
Dr. Chrzanowska studies the function and malfunction of blood vessels and the endothelial cells that line them. When blood vessels and endothelium function properly, they aid in the basic processes that ensure human health, like regulating blood pressure, forming and oxygenating tissues, and healing wounds. But when endothelium is not healthy and isn’t able to sense the flow of blood as it usually does, or is exposed to damaging factors, patients are at risk for diseases like hypertension and cardiovascular disease. “The health of blood vessels impacts all aspects of human life,” Dr. Chrzanowska said.
Understanding the processes that cause cells to function is important to human health, but investigators still don’t know how they all work together. Dr. Chrzanowska believes that endothelial cells and their molecules are the key to understanding cardiovascular disease, the leading cause of death for men and women of most racial and ethnic groups in the U.S. “Each cell will have upwards of 3,000 different molecules, and each one has a different function,” she said. “But they can be grouped into proteins that provide structure and proteins that are involved in communication, or biochemical signaling. We are interested in one particular class of molecules that are involved in transmitting those signals.” She and her team discovered that the molecule they are studying—RAP1—is important in the regulation of blood pressure and the formation of blood vessels.
“Our lab is contributing a unique piece of the puzzle to understanding how this all works,” she said. One upcoming study pertains to heart failure and how endothelium in the cardiac muscle affects the heart’s health. “It’s known that if there are unhealthy changes in the muscle cells themselves, that will lead to heart disease and heart failure,” she said. Dr. Chrzanowska and her team recently found that when the RAP1 molecule is inactive in laboratory models, heart failure is often present. A related research topic in her lab is the recognition that capillaries in the heart are lined with endothelium. The functionality of these micro-vessels in the heart affects its health and function, and RAP1 is required for healthy functionality.
“If we understand what goes wrong at the molecular level, we can prevent it,” Dr. Chrzanowska said. “Once we diagnose a defect or damage to endothelium, we can try to repair it by promoting the activity of the factors that enhance endothelial function.” RAP1 promotes the formation of blood vessels, so if investigators understand how it works and what causes it to malfunction, they can target it and develop new treatments for patients at risk for cardiovascular disease and other conditions.
About the expert: Madgalena Chrzanowska, PhD, FAHA, is an investigator at Versiti Blood Research Institute and associate professor in the Department of Pharmacology & Toxicology at the Medical College of Wisconsin.