Research Highlight July 14, 2020

How to heal a heart

JAX Professor and Scientific Director Nadia Rosenthal

Rosenthal joins international team to study the immune system’s effects on the heart’s connective tissue.

Every organ and system of the body contains components of the immune system, and they’re there to fight infections, heal injuries and otherwise maintain health. Typically, immune cells promote healing by triggering inflammation and then turning it off. But in the heart, the immune response remains unchecked, stimulating a fibrotic response that greatly impairs the heart’s function.

Heart researcher Nadia Rosenthal, Ph.D., F.Med.SciGlobal leader in the use of targeted mutagenesis in mice to investigate muscle development, disease and repair.Nadia Rosenthal, Ph.D., and colleagues have shown that the heart contains a large population of immune cells called macrophages. “The problem is,” says Rosenthal, who is professor and scientific director of mammalian genetics at The Jackson Laboratory (JAX), “the immune system does not respond to damage in the adult heart as it does in other tissues.”

When the heart is injured, she says, “the immune cells—including macrophages, monocytes and dendritic cells—flood into the heart and wreak havoc. They stimulate resident fibroblasts to make scar tissue, which impairs the heart’s contractile function.” Cardiac fibrosis is associated with nearly all forms of heart disease, according to the American Heart Association.

The Paris-based Leducq Foundation is providing funding for Rosenthal and collaborators from institutions in the U.S., Germany and England to zero in on the immune regulation of cardiac fibrosis  with the goal of translating their findings into new diagnostics and therapeutics, a five-year project totaling $6.5 million. “The idea behind this grant is to explore the emerging importance of the interaction between the immune system and the structure of connective tissue of the heart in health and disease,” Rosenthal says.

Besides her lab at JAX, Rosenthal runs a research program in the Imperial Centre for Translation and Experimental Medicine at Imperial College, London, where she also holds a chair in cardiovascular science. Elvira Forte, Ph.D., of JAX and Susanne Satler, Ph.D., of Imperial College are on the Leducq grant team.

The grant, which starts in January 2021, is part of Leducq’s highly competitive and prestigious Transatlantic Networks of Excellence in Cardiovascular and Neurovascular Research initiative, which aims to foster scientific innovation by bringing together international teams of researchers with complementary expertise and resources to work together on a common thematic problem. 

Rosenthal says this team approach will be extremely helpful in making progress in understanding the heart-immune connection. “This Leducq network brings together some of the  best minds in the fields of cardiovascular disease and immunology,” she says. “I'm honored and delighted to be part of the team.”