Researchers awarded $1.5 million each to help uncover breakthrough in heart-health research

Two researchers have been awarded grants that could help uncover the next breakthrough in heart-health research, the American Heart Association and The Paul G. Allen Frontiers Group announced Wednesday.

Suneel Apte at the Cleveland Clinic and Jeffrey Holmes at the University of Virginia have been awarded $1.5 million each to study the extracellular matrix -- what scientists call the "natural glue" that holds tissues and organs together. However, recent evidence suggests that the extracellular matrix plays a much more central role in everything from aging to tissue repair to cell-to-cell communication. These dynamic aspects of the extracellular matrix remain understudied relative to other aspects of cardiovascular biology.

"With these grants, we are trying to go beyond traditional research approaches and reward out-of-box thinking," said Ivor Benjamin, M.D., professor and director of the Cardiovascular Center at Froedtert & Medical College of Wisconsin. Benjamin, who is also the AHA's president-elect and immediate past research committee chairman, helped select the two projects for funding.

Tom Skalak, Ph.D., Executive Director of The Paul G. Allen Frontiers Group, said the organizations sought an uncommon approach to fight heart disease.

"Our shared feeling with the American Heart Association was that it was desirable to take a serious look at areas of cardiovascular knowledge outside of the most common approaches to heart health and disease," Skalak said. "That paved the way for this new work on extracellular matrix, and perhaps to a new era of heart health for millions of people. We're very excited about that prospect."

Suneel Apte, M.B.B.S., D. Phil, said architecture helps describe his work.

"If our body is a building, the cells are the bricks and the extracellular matrix, which binds cells together, is the mortar," said Apte, biomedical engineering researcher at the Cleveland Clinic Lerner Research Institute. "Unlike mortar in a wall, extracellular matrix is not still but constantly moving and changing. It is continuously being broken down and rebuilt by cells of the heart and blood vessels, but this process is poorly understood."

Apte's research team will study how and why breakdown occurs normally, and how it may contribute to heart development and vascular disease. Too much extracellular matrix breakdown is harmful because it weakens the structure, and cells rely on correct extracellular matrix composition and quantity for health-giving information.

"Instead of timidly looking brick by brick at the mortar, we propose using new technology to take in all the changes in the tissues at one fell swoop," Apte said. "Ultimately, we hope our approach will find novel disease markers and targets to develop drugs that will treat cardiovascular disease."

Jeffrey Holmes, M.D., Ph.D., professor of Biomedical Engineering and Medicine at University of Virginia, Charlottesville, said his research will bring together investigators and methods from bioengineering, immunology, physiology and chemistry to study when, where and how information is encoded into the extracellular matrix.

"Many extracellular matrix proteins persist for years or decades, accumulating biochemical changes that fundamentally change tissue properties," Holmes said. "Thus, much of the information about long-term processes such as aging is stored in the extracellular matrix and read back by new cells as they arrive."

To understand how information is stored in the ECM, Holmes and his team will consider how proteins are deposited, how rapidly they turn over, what role aging plays in these changes, and how these changes influence cell-matrix interactions.

This joint endeavor leverages the combined strength of the American Heart Association, with renowned expertise in cardiovascular research, and The Paul G. Allen Frontiers Group, which supports pioneering scientific explorers with the potential to transform cardiovascular medicine.