Researchers at the Victor Chang Cardiac Research Institute in Australia have developed an unprecedented integrated map of heart cells, shedding light on the processes behind cardiac fibrosis—a leading cause of heart failure. This innovative map lays the foundation for the development of precision drugs designed to prevent the scarring damage that occurs after a heart attack. When a heart attack strikes, it causes damage to the heart’s muscles, resulting in scar tissue that lacks the elasticity and contractility of healthy muscle. This permanent damage diminishes the heart’s ability to pump blood efficiently, often leading to heart failure.
Professor Richard Harvey led the study in collaboration with Dr Ralph Patrick and Dr Vaibhao Janbandhu from the institute. Professor Harvey emphasized that the research marks a significant advance in understanding cardiac fibrosis, which is prevalent in various heart diseases, including those exacerbated by high blood pressure. He pointed out the considerable investments in finding new drugs to control cardiac fibrosis, which have been mainly unsuccessful, underscoring the urgent need for innovative treatments capable of halting or even reversing this condition.
Professor Harvey explained that while fibrosis is a natural healing process of the body, in the heart, it can become excessive due to unresolved disease triggers, leading to scarring that severely impairs heart function and becomes a primary cause of heart failure. The team employed state-of-the-art technology to analyze gene expression in single cells. This allowed them to delineate the progression of cellular states involved in cardiac fibrosis and how these evolve. Their methodology involved analyzing RNA signatures from 100,000 individual cells, focusing on those involved in fibrosis, and integrating this data with findings from various pioneering studies on different heart conditions.
This comprehensive approach enabled the creation of an intricate cellular map of a mouse model heart, pinpointing cells and pathways that play roles in fibrosis. The researchers identified various cellular states, including resting, activated, inflammatory, and progenitor cells, as well as dividing cells and specialized cells known as myofibroblasts and matrifibrocytes. They discovered that myofibroblasts, which are absent in healthy hearts but are believed to drive scarring, begin to form three days after a heart attack, peaking on the fifth day and then transitioning into matrifibrocytes, which potentially hinder the scar’s resolution.
The findings, published in Science Advances, also explored heart disease models such as heart failure induced by conditions like hypertension due to aortic stenosis. Dr Janbandhu noted a surprising similarity in the progression of fibrosis across different types of heart diseases, with myofibroblasts appearing early on during hypertension and then transitioning into matrifibrocytes, similar to their behaviour after a heart attack. This discovery opens the doors to future therapies that could target specific cell types or processes across various heart conditions, offering hope for preventing permanent damage to healthy cells and improving patient outcomes.
The study, which utilized data from both mouse models and human patients, indicates that heart failure in humans can evolve over decades. This underscores the importance of regular monitoring and effective management of blood pressure, a major risk factor for severe heart conditions. Dr Janbandhu’s emphasis on the treatable nature of persistent high blood pressure and the potential to prevent devastating consequences through proactive management should inspire a sense of responsibility and proactivity in the audience.
More information: Ralph Patrick et al, Integration mapping of cardiac fibroblast single-cell transcriptomes elucidates cellular principles of fibrosis in diverse pathologies, Science Advances. DOI: 10.1126/sciadv.adk8501
Journal information: Science Advances Provided by Victor Chang Cardiac Research Institute
