NIH awards grant to study how dilated cardiomyopathy progresses to heart failure

A University of Arizona College of Medicine – Phoenix researcher was recently awarded a $1.9 million National Institutes of Health grant to study the molecular mechanisms of how dilated cardiomyopathy progresses to heart failure, which could eventually lead to better preventive and treatment options for heart failure.

Heart failure is inextricably linked with dilated cardiomyopathy, or DCM, a disease characterized by the progressive enlargement of the heart and reduced contractility reflected by reduced ejection fraction. Symptomatic heart failure with reduced ejection is an irreversible condition with an approximately 50% death rate within five years of diagnosis and cardiac transplantation as the only cure.

Inna Gladysheva, PhD, a research professor in the Department of Internal Medicine and a member of the Translational Cardiovascular Research Center at the College of Medicine – Phoenix, will use the grant to advance her research into the impact of proteolytic enzymes' networks in the progression of DCM to overt heart failure and examine how the protease-driven impairment of neurohumoral biological pathways impacts this progression.

The project aims to elucidate the regulatory role of the upstream proteolytic network in renin-angiotensin-aldosterone system overactivation and the pathophysiology of heart failure, ultimately leading to better treatment options than solely full heart transplantation.

"Our exciting discovery suggests and offers a new paradigm in heart failure management. The long-term project goal is to translate knowledge into novel therapeutic strategies needed to prevent or treat the progression of heart failure, improving its outcomes and the duration of patients' lives," Gladysheva said.

A major sign in DCM progressing to symptomatic heart failure is edema, where fluid builds up in the lungs or systemically. People with edema may experience breathlessness, disability and, sometimes, death. 

We also investigate the impacts of pharmacological and non-pharmacological approaches such as lifestyle choices on cardiac function and edema with presided consideration of sex and age-related differences. Our translational studies contribute to understanding the molecular mechanisms forcing the progression of cardiac dysfunction and edema development. Importantly, they also suggest that lifestyle choices can play a significant role in preventing heart failure development in patients with DCM or at risk of DCM."

Inna Gladysheva, PhD, research professor, Department of Internal Medicine and member of the Translational Cardiovascular Research Center, College of Medicine – Phoenix

According to the Heart Failure Society of America, 6.7 million Americans over the age of 20 have heart failure, and the prevalence is expected to rise to 8.5 million Americans by 2030. With statistics estimating that 1 in 4 people will develop heart failure in their lifetime, more effective therapeutics are crucial to stemming the disease's effects.

"I am deeply thankful to my incredible colleagues and collaborators – Guy Reed, MD, MS, Ryan Sullivan, DVM, LATG, Sofiyan Saleem, PhD, and others – whose unique, complementary expertise helped sharpen an idea to hypothesis-based evidence supporting this award."