There currently is no effective therapy for coronary artery disease, which is a precursor to ischemia and myocardial infarction, or heart attack. Researchers at the University of Arizona College of Medicine – Phoenix are seeking to change that, thanks to a $3.7 million, five-year grant from the National Heart, Lung and Blood Institute, a division of the National Institutes of Health.
Coronary artery disease is the most common form of heart disease, the leading cause of death for both men and women. Of the roughly 695,000 people who died from heart disease in 2021, more than 375,000 deaths were attributable to coronary artery disease, according to the Centers for Disease Control and Prevention.
The grant will support Shirin Doroudgar, PhD, an assistant professor in the Department of Internal Medicine and member of the Translational Cardiovascular Research Center, as she aims to identify proteins that could serve as new therapeutic targets to help the heart recover post-heart attack or ischemia.
Until now, many studies have focused on the genetics of heart disease. But researchers now know that understanding the proteins encoded by the genes and what determines the levels of those proteins, a process called protein homeostasis, is what determines how well the heart functions, especially in the setting of heart disease.
“Since it is a critical determinant of cell and organism health, my research focuses on identifying key molecular regulators of protein homeostasis,” Doroudgar explained. “Disease and age-related impairments in protein homeostasis occur in many forms of cardiovascular disease. In the heart, such impairments can lead to cardiac myocyte (muscle cell) dysfunction and eventually myocyte death, a particularly damaging result, given that cardiac muscle, which is required to pump blood effectively, cannot regenerate or heal itself once it is damaged by a heart attack.”
The CDC reports that more than 6.5 million Americans over the age of 20 are in danger of heart failure, a condition explicitly linked to coronary artery disease. With half of all patients dying within five years of diagnosis, access to more effective therapies is crucial.
“There is a pressing need for treatments that help cardiac myocytes survive a heart attack, as their survival is required to avoid decreases in heart function, or heart failure, which is a fatal condition with no cure,” Doroudgar said.
Doroudgar and her team are seeking to identify what maintains protein homeostasis in ways that fortify cardiac myocytes, the cells in the heart that are critical for its pumping function. Then, they can use that information to design new drugs that could potentially protect the heart.
“The long-term goal of my lab is to better understand the age- and disease-linked changes in protein homeostasis that contribute to heart disease, and to use this understanding to design new therapies to reduce the deleterious effects of age and disease on the function of the heart,” she said.
“Dr. Doroudgar’s research is groundbreaking, as it will identify new potential therapies for heart disease that could revolutionize clinical treatment and save many lives in the future,” said Christopher Glembotski, PhD, the vice dean of research, director of the TCRC and a professor of internal medicine at the College of Medicine – Phoenix.
