By AMERICAN HEART ASSOCIATION NEWS
Tiny cells in your heart and blood vessels are constantly on the move, darting in and out of microscopic structures that look a little like scaffolding around buildings.
That might sound like run-of-the-mill activity, but scientists say figuring out exactly what the scaffolding does to cells and how it redirects their activity just may help prevent heart disease and stroke, the two leading causes of death in the world.
On Wednesday, two researchers received $1.5 million each to delve deeper into these minute interactions as part of a joint award from the American Heart Association and The Paul G. Allen Frontiers Group. Jeffrey Holmes, M.D., Ph.D. at the University of Virginia, and Suneel Apte, M.B.B.S., D.Phil. with the Cleveland Clinic, are hopeful about their exploration of this tiny environment.
They’re studying what’s known as the “extracellular matrix,” a technical term for the scaffolding-like structures that surround the heart’s cells and tell them where to go and what to do. This scaffolding is also the material that holds everything together in the heart and blood vessels and determines their structural strength.
“Heart disease stems from an accumulation of many small changes over years,” Holmes said. “The goal is to detect and correct problems before they become serious, preventing as many cases of heart disease and stroke as possible.”
Holmes says the matrix is somewhat like a school, with the cells like students. The problem is, those classrooms have been secretive; we don’t understand enough about how information flows inside them.
“Our goal is to find out which books each student reads, which teachers they interact with and what they are learning, so we can understand what is happening in the school and how to improve outcomes,” said Holmes, professor of Biomedical Engineering and Medicine and director of the Center for Engineering in Medicine at the University of Virginia in Charlottesville.
His team will look at how information storage and retrieval changes with aging, with an aim to develop better therapies for chronic diseases. Apte will examine how remodeling the extracellular matrix, much like remodeling a house — breaking down walls, rearranging and replacing plumbing — may contribute to heart development and vascular disease. While scientists often adopt a “brick-by-brick” method in their research, Apte favors a sweeping approach that will examine all the changes in the tissues at once.
“One of the major ways in which cells remodel the matrix is by producing enzymes called proteases,” Apte said. “These ‘molecular scissors’ can cleave at precise places in many molecules, but we know very little about which molecules they attack and the consequences of their activity.”
A clearer view of what’s happening in the heart and blood vessels could help shed light on that molecular activity.
“We can work backward, sideways and forward from there to understand which protease undertakes which activity, how it contributes to causing disease, find new disease markers for diagnostics and identify new drug targets,” Apte said.
Experts say better understanding how the matrix instructs cells to behave and how it stores long-term memory could help advance the fight against heart disease and stroke, which kill about 2,200 Americans a day.
Tom Skalak, Ph.D., executive director of The Paul G. Allen Frontiers Group, a division of the Seattle-based Allen Institute, said the AHA and the Allen Group’s uncommon approach is an exciting way to tackle heart disease mysteries, with the collaboration leading to great possibilities.
“It has paved the way for this new work on extracellular matrix, and perhaps to a new era of heart health for millions of people,” Skalak said. “We’re very excited about that prospect.”
Ivor Benjamin, M.D., immediate past chairman of the AHA’s research committee, said such research is critical to moving beyond current thinking about cardiovascular diseases.
“Many of our current therapies merely manage the situation, but they’re not curative,” said Benjamin, professor and director of the Cardiovascular Center at Froedtert Hospital & Medical College of Wisconsin, and the AHA’s president-elect. “Our goal was to step outside of the traditional way of funding awards and find investigators working on innovative approaches.”