NIH Awards U of A $2.16 Million to Study Heart Scarring

Imagine the heart like a balloon, expanding as it fills with blood and then contracting as it pushes that blood out to the body. If someone's heart muscle gets weak and cannot pump as much blood, they suffer from heart failure with reduced ejection fraction, also known as systolic heart failure. 

The National Institutes of Health awarded a $2.16 million grant to Will Richardson, University of Arkansas associate professor in the Ralph E. Martin Department of Chemical Engineering, to study the causes of heart failure with reduced ejection fraction, develop personalized treatments and identify promising medications that could treat the condition. 

For the work, Richardson has partnered with Dr. Michael Zile, a practicing cardiologist and Distinguished University Professor of Cardiology at the Medical University of South Carolina (MUSC) as well as Dr. Amy Bradshaw, a matrix biologist and professor of cardiology at MUSC. 

Some patients with serious damage need a device implanted to help their hearts pump blood, called a left ventricular assist device, or LVAD. 

"These are patients that are really at the end of the proper function of their heart," Richardson said. "Once they get this LVAD, they need it for the rest of their life or until they get a new heart transplant." 

Zile and Bradshaw will provide tissue and blood samples from patients with LVADs, and Richardson will grow cells from those samples and test them in his Fayetteville lab. 

Fibrosis, or scar tissue, can build up in the heart after a heart attack or due to stress from high blood pressure. The fibrosis can interrupt electrical signals and mechanical function in the heart. The first aim of Richardson's project is to better understand how collagen fibers build up in a damaged heart. 

In his lab, Richardson uses patent-pending petri dishes that he developed to mechanically stimulate the cells. Because the cells come from individual patients, he can test how an individual's tissue responds. 

"We can stretch and pull these cells in a way that maps back to how they get stretched in the heart of a patient," Richardson said. 

Richardson also created a complex computer model that simulates roughly 150 signaling nodes in the heart that pass along biological messages. The model incorporates thousands of variables, and it allows researchers to understand which biomarkers predict fibrosis and how patients will respond to treatments. 

"We're starting out not with an AI framework, but a network that's already been established in biology and is fully explainable. We just turn that into math," he said. 

The model also allows Richardson to virtually test drugs and combinations of drugs. 

"The model computationally is really important when you start talking about combinations of drugs, because there are millions of different combinations. We don't have the time, money or resources to screen that many things." 

The model can narrow down the drugs or combination of drugs that could be effective and then the researchers can test them experimentally. 

The model could also flag molecules that a drug could switch on or off to slow the damage, even when no such drug exists yet. Those results could motivate pharmaceutical companies to create new drugs to control those processes. 

The four-year grant was awarded by the NIH's National Heart, Lung and Blood Institute.