Scientists test way to stop heart damage after cardiac injury

September 28, 2017
The microscopic image on left shows a control mouse heart cross section after simulated cardiac injury with significant fibrosis. The image the right shows the "experimental model" in which Wnt/b-catenin was inhibited in the hearts of mice, resulting in reduced fibrosis. Scientists report early research results in Nature Communications that suggest scientists might be on to a way to preserve cardiac function after heart attacks or for people with certain inherited heart defects. Credit: Cincinnati Children's

Early research results suggest scientists might be on to a way to preserve heart function after heart attacks or for people with inherited heart defects called congenital cardiomyopathies.

Researchers at the Cincinnati Children's Heart Institute report Sept. 28 in Nature Communications that after simulating heart injury in laboratory mouse models, they stopped or slowed cardiac , organ enlargement and preserved by blocking a well-known molecular pathway.

The Wnt/β-catenin signaling pathway is involved in several of the body's fundamental biological processes. After heart injury, however, Wnt/β-catenin signaling ramps up in cardiac fibroblast cells to cause fibrosis, scarring and harmful enlargement of the heart muscle, according to the researchers.

"Our findings provide new insights on what causes cardiac fibrosis and they open the potential for finding new therapeutic approaches to fight it and preserve heart ," says Katherine Yutzey, PhD, lead study author and scientist in Molecular Cardiovascular Biology. "Wnt/β-catenin signaling is involved in many normal and disease processes and it's tough to target therapeutically. But the idea that early targeting of fibrotic response in cardiac disease may improve muscle function and stop disease is an exciting new direction."

Heart disease is one of the leading killers of people in the United States, according to the U.S. Centers for Disease Control. And a growing number of adults who were treated for congenital heart malformations as children - many who essentially had their hearts reconstructed - face lifelong potential health complications as a result.

Adult is a growing priority and area of scientific inquiry at Cincinnati Children's. Clinicians and researchers at the medical center are developing new clinical and research strategies for adults who were pediatric heart patients. This includes looking for what so far are elusive therapeutic strategies to repair scarred and poorly functioning heart tissues after cardiac injury or .

Mice Help Show the Way

In the current study, Yutzey and her colleagues used a newly developed line of genetically bred laboratory that allowed them to determine how important Wnt/β-catenin signaling is in cardiac fibroblast cells. Fibroblasts are important to building the connective tissues and structural framework cells that help hold the body together. But in the context of , researchers are learning resident cardiac fibroblast cells cause a deadly mix of tissue fibrosis, scarring and diminished function.

To simulate cardiac injury in the mice, researchers conducted a procedure called trans-aortic constriction to restrict blood flow through the heart. Some of the mice were bred so that following cardiac injury they did not express cardiac Wnt/β-catenin in fibroblasts. Control mice in the study continued to express Wnt/β-catenin following heart injury.

The control mice exhibited extensive fibrosis, scarring and diminished heart function. Mice not expressing Wnt/β-catenin had diminished fibrosis and scarring and the animals' heart function was preserved.

Study authors stress the laboratory research is still at an early stage and it is too early to know to what extent it might apply to actual clinical treatment. But the findings of this study, and other papers involving different molecular pathways by other research teams, have intensified interest in understanding how inhibiting cardiac fibrosis improves muscle cell function and pathology.

This will be a central question in future research fibrosis studies by Yutzey and her colleagues, along with looking for possible ways to target the Wnt/β-catenin signaling pathway for potential therapeutic benefit.

Explore further: Study hints at experimental therapy for heart fibrosis

More information: Fu-Li Xiang et al, Loss of β-catenin in resident cardiac fibroblasts attenuates fibrosis induced by pressure overload in mice, Nature Communications (2017). DOI: 10.1038/s41467-017-00840-w

Related Stories

Study hints at experimental therapy for heart fibrosis

August 14, 2017
Researchers report encouraging preclinical results as they pursue elusive therapeutic strategies to repair scarred and poorly functioning heart tissues after cardiac injury—describing an experimental molecular treatment ...

How Gata4 helps mend a broken heart

August 15, 2017
During a heart attack, blood stops flowing into the heart; starved for oxygen, part of the heart muscle dies. The heart muscle does not regenerate; instead it replaces dead tissue with scars made of cells called fibroblasts ...

Root of cardiac fibrosis defined

July 13, 2017
Northwestern Medicine scientists have identified a novel molecular mechanism that regulates scar formation in the heart, a common manifestation of aging and nearly every form of heart disease. The discovery was published ...

A pathway controlling inflammatory responses aids recovery after heart attack

February 6, 2017
After a heart attack, or myocardial infarction, a patient's long-term prognosis depends on the ability of the heart tissue to heal and remodel. Immune system activation and inflammatory responses that occur in the aftermath ...

Scientists identify protein linked to chronic heart failure

May 26, 2017
Researchers in Japan have identified a receptor protein on the surface of heart cells that promotes chronic heart failure. The study, "Corticotropin releasing hormone receptor 2 exacerbates chronic cardiac dysfunction," which ...

Cardiac stem cells from heart disease patients may be harmful

June 15, 2017
Patients with severe and end-stage heart failure have few treatment options available to them apart from transplants and "miraculous" stem cell therapy. But a new Tel Aviv University study finds that stem cell therapy may, ...

Recommended for you

How genes and environment interact to raise risk of congenital heart defects

October 19, 2017
Infants of mothers with diabetes have a three- to five-fold increased risk of congenital heart defects. Such developmental defects are likely caused by a combination of genetic and environmental factors. However, the molecular ...

Mouse studies shed light on how protein controls heart failure

October 18, 2017
A new study on two specially bred strains of mice has illuminated how abnormal addition of the chemical phosphate to a specific heart muscle protein may sabotage the way the protein behaves in a cell, and may damage the way ...

Newborns with trisomy 13 or 18 benefit from heart surgery, study finds

October 18, 2017
Heart surgery significantly decreases in-hospital mortality among infants with either of two genetic disorders that cause severe physical and intellectual disabilities, according to a new study by a researcher at the Stanford ...

Saving hearts after heart attacks: Overexpression of a gene enhances repair of dead muscle

October 17, 2017
University of Alabama at Birmingham biomedical engineers report a significant advance in efforts to repair a damaged heart after a heart attack, using grafted heart-muscle cells to create a repair patch. The key was overexpressing ...

Physically active white men at high risk for plaque buildup in arteries

October 17, 2017
White men who exercise at high levels are 86 percent more likely than people who exercise at low levels to experience a buildup of plaque in the heart arteries by middle age, a new study suggests.

High blood pressure linked to common heart valve disorder

October 17, 2017
For the first time, a strong link has been established between high blood pressure and the most common heart valve disorder in high-income countries, by new research from The George Institute for Global Health at the University ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.