Loyola Medicine Physiologist Authors Study That Could Lead to New Heart Failure Drugs | Heart & Vascular | Loyola Medicine
Monday, February 8, 2016

Loyola Medicine Physiologist Authors Study That Could Lead to New Heart Failure Drugs

MAYWOOD, Il. (Feb. 8, 2016) - In a finding that could lead to new drugs to treat heart failure, researchers have uncovered the molecular mechanism that regulates how the heart pumps blood.

The key molecular player in this mechanism is a giant protein called titin, according to a study led by senior author Pieter de Tombe, PhD, of Loyola University Chicago Stritch School of Medicine. The study was published Feb. 8, 2016, in Proceedings of the National Academy of Sciences.

De Tombe is interim vice dean for research and chair of the Department of Cell and Molecular Physiology at Loyola University Chicago Stritch School of Medicine.

A healthy heart regulates itself so that with each beat, it pumps out as much blood as it receives. When blood enters the heart, it stretches the wall of the pumping chamber, triggering muscle to contract and pump blood out. This regulatory-control mechanism is known as the Frank-Starling law, named after physiologists Otto Frank and Ernest Starling.

In heart failure patients, the Frank-Starling law breaks down. Heart muscle becomes too weak to pump out of the heart the same amount of blood that flows into the heart. To compensate, the heart enlarges, develops more muscle mass and beats faster. But eventually these compensatory measures fall short. The heart cannot pump enough blood to meet the body’s needs for blood and oxygen, leading to shortness of breath, fatigue, weakness, swelling in legs, fluid retention and other symptoms.

The study by de Tombe and colleagues found that the titin protein is key to understanding the Frank-Starling mechanism and therefore how much blood the heart is able to pump out with each beat. Titin is an essential component of muscle. It’s the largest protein in the body, weighing about 15 times as much as an average protein. In the heart, it acts like a spring, affecting the heart’s ability to contract and relax. Normally when people age, the titin protein gets shorter. But in heart failure patients, the protein grows longer and becomes less effective.

“Our findings provide insights into the molecular basis of the Frank-Starling regulatory mechanism,” de Tombe said. “This will help clarify the field and could point the way to new medications to more effectively treat heart failure. We were able to eliminate a number of other competing theories, including some of our own.”

About 5.1 million people in the United States have heart failure, and heart failure is listed as a contributing cause in one out of nine deaths, according to the Centers for Disease Control and Prevention. About half of heart failure patients die within five years of diagnosis. Heart failure costs the nation about $32 billion each year, including healthcare costs and missed days of work.

The study is titled “Titin strain contributes to the Frank-Starling law of the heart by structural rearrangements of both thin-and thick-filament proteins.” It was funded in part by grants from the National Institutes of Health.

De Tombe’s co-authors are Younss Ait-Mou, Karen Hsu, Gerrie Farman and Mohit Kumar of Loyola University Chicago Stritch School of Medicine; Thomas Irving of the Illinois Institute of Technology; and Marion Greaser of the University of Wisconsin.

About Loyola Medicine and Trinity Health

Loyola Medicine, a member of Trinity Health, is a quaternary care system based in the western suburbs of Chicago that includes Loyola University Medical Center (LUMC), Gottlieb Memorial Hospital, MacNeal Hospital and convenient locations offering primary and specialty care services from 1,877 physicians throughout Cook, Will and DuPage counties. LUMC is a 547-licensed-bed hospital in Maywood that includes the William G. and Mary A. Ryan Center for Heart & Vascular Medicine, the Cardinal Bernardin Cancer Center, a Level 1 trauma center, Illinois's largest burn center, a certified comprehensive stroke center and a children’s hospital. Having delivered compassionate care for over 50 years, Loyola also trains the next generation of caregivers through its teaching affiliation with Loyola University Chicago’s Stritch School of Medicine and Marcella Niehoff School of Nursing. Gottlieb is a 247-licensed-bed community hospital in Melrose Park with 150 physician offices, an adult day care program, the Gottlieb Center for Fitness, the Loyola Center for Metabolic Surgery and Bariatric Care and the Loyola Cancer Care & Research at the Marjorie G. Weinberg Cancer Center at Melrose Park. MacNeal Hospital is a 374-bed teaching hospital in Berwyn with advanced inpatient and outpatient medical, surgical and psychiatric services, advanced diagnostics and treatments. MacNeal has a 12-bed acute rehabilitation unit, a 25-bed inpatient skilled nursing facility, and a 68-bed behavioral health program and community clinics. MacNeal has provided quality, patient-centered care to the near west suburbs since 1919.

Trinity Health is one of the largest multi-institutional Catholic healthcare systems in the nation, serving diverse communities that include more than 30 million people across 22 states. Trinity Health includes 94 hospitals, as well as 109 continuing care locations that include PACE programs, senior living facilities and home care and hospice services. Its continuing care programs provide nearly 2.5 million visits annually. Based in Livonia, Mich., and with annual operating revenues of $18.3 billion and assets of $26.2 billion, the organization returns $1.1 billion to its communities annually in the form of charity care and other community benefit programs. Trinity employs about 133,000 colleagues, including 7,800 employed physicians and clinicians. Committed to those who are poor and underserved in its communities, Trinity is known for its focus on the country's aging population. As a single, unified ministry, the organization is the innovator of Senior Emergency Departments, the largest not-for-profit provider of home health care services—ranked by number of visits—in the nation, as well as the nation’s leading provider of PACE (Program of All Inclusive Care for the Elderly) based on the number of available programs.