Cardiac mapping to prevent damage from heart attacks

Scientists at Australia’s Victor Chang Heart Institute have created the first integrated map of cardiac cells that sheds light on the process of cardiac fibrosis, a major cause of heart failure.

The discovery opens new avenues for the development of targeted drugs to prevent the scarring damage that occurs after a heart attack.

During and after a heart attack, heart muscle is damaged and scar tissue forms that lacks the elasticity and contractile strength of healthy heart muscle. This damage is permanent, affecting the heart’s ability to pump blood and ultimately leading to heart failure.

Professor Richard Harvey, who led the research with Dr Ralph Patrick and Dr Vaibhao Jambandhu from the Institute, said the discovery was a major step forward in understanding cardiac fibrosis, which accompanies almost all heart diseases, including the strain on the heart caused by high blood pressure.

“Millions, if not billions, of dollars have been poured into developing new drugs to inhibit cardiac fibrosis over the years, but these efforts have largely failed. There is an urgent need to develop new therapies that can halt or reverse cardiac fibrosis and benefit millions of people,” Prof Harvey said.

“Fibrosis is an essential part of the body’s healing process. But in the heart, if disease triggers are not addressed, fibrosis can progress too far and lead to scarring that is very detrimental to cardiac function and is the leading cause of heart failure.”

“Using innovative techniques that allow us to analyse gene expression in single cells, we were able to elucidate for the first time the progressive cellular states involved in cardiac fibrosis and how these cells evolve from day to day.”

The research team analysed RNA signatures from 100,000 single cells, focusing on those involved in fibrosis, and integrated data from several pioneering studies of different cardiac disease conditions.

This enabled them to generate an integrated cellular map of mouse model hearts that pinpoints the cells and pathways involved in fibrosis.

The study identified resting cells, activated cells, inflammatory cell populations, progenitor cell pools, dividing cells, and specialized cells called myofibroblasts and matrix fibrocytes.

The study found that myofibroblasts, which are thought to be the main driver of scar formation but are not present in healthy hearts, begin to form in mouse models three days after a heart attack and peak at day five. The fibroblasts then break down into a form called matrifibrocytes, which may impede scar resolution.

This study Scientific advanceswe also investigated another cardiac model: aortic stenosis, i.e., heart failure induced by high blood pressure in the body as a result of hypertension.

“We found striking similarities in the progression of fibrosis in very different types of heart disease. Myofibroblasts are abundant early in hypertension and then break down into matrifibrocytes, just as they do after a heart attack,” said Dr. Vaibhao Jambandhu.

“This paves the way for future therapies that target specific cell types and processes in various heart diseases, which will hopefully prevent healthy cells from being permanently damaged.”

The study used data from both mouse models and human patients, and because heart failure can take decades to progress in humans, the precise cell types and timing of processes in human patients require more detailed investigation.

“Persistent hypertension can have dire consequences, but it is treatable and emphasises the need to monitor and rapidly control hypertension,” Dr Jambandhu added.

The research team also created a resource web tool for researchers around the world, called CardiacFibroAtlas, which allows users to visualize and analyze the role of genes in heart attacks and related health problems.

Courtesy of Victor Chang Heart Research Institute