“For the first time, using revolutionary technology that enables to analyse gene expression in single cells, we have been able to map out the progressive cell states involved in cardiac fibrosis and how these cells evolve day-by-day.”
-Prof Richard Harvey, Study Leader
The research team at the Victor Chang Cardiac Research Institute in Australia, led by Prof Richard Harvey along with Dr Ralph Patrick and Dr Vaibhao Janbandhu, analysed the RNA obtained from 100,000 single cells that were part of fibrosis. Data were collectively integrated from several studies pioneering on various states of heart disease. This has led to the production of a cellular mapping of a mouse model of the heart that marks the cellular pathways involved in fibrosis. This study was identifying the resting cells, the activated cells, an inflammatory population, a progenitor pool, the dividing cells, and the specialised cells that are called the myofibroblasts and the matrifibrocytes.
This study was published in the journal Science Advances. It also included the exploration of other heart disease models of heart failure that were induced by high internal blood pressures, due to aortic stenosis or even hypertension. This discovery is believed to open up doors to develop targeted therapeutic drugs that cause prevention of scarring and damage caused after a heart attack. When a heart attack occurs and afterward, the heart muscles are damaged, that induces the formation of scarring, causing lack of the elasticity and contractility that a healthy heart muscle possesses. This type of damage is permanent and deteriorates the heart’s ability to pump blood resulting in heart failure.
The mouse models and human patients were inclusive of this study. Heart failure in humans takes decades to evolve, so exact cell types and processes timings’ need further exploration in detail. The team has also come up with the ‘CardiacFibroAtlas’, a resource web tool that aids researchers worldwide. It shows users a visualisation and analyses how the genes behave in heart attacks and health-related problems. Prof Richard Harvey continues to add that the discovery is a major step forward in understanding cardiac fibrosis-which accompanies virtually all forms of heart disease including the overloading of the heart due to high blood pressure.
“Millions if not billions of dollars have been poured into seeking new drugs to control cardiac fibrosis over the years, but these efforts have largely failed. There is an urgent need to develop novel treatments that could arrest or even reverse cardiac fibrosis, benefitting millions. Fibrosis is an essential part of the body’s way of healing. But in the heart, if the disease triggers are not resolved, the process can go too far, causing scarring that is incredibly harmful to heart function and a major cause of heart failure. For the first time, using revolutionary technology that enables us to analyse gene expression in single cells, we have been able to map out the progressive cell states involved in cardiac fibrosis and how these cells evolve day-by-day.”
Dr Vaibhao Janbandhu adds, “We found a surprising similarity in fibrosis progression in very different types of heart diseases. Myofibroblasts were abundant dearly on during hypertension and then resolved into matrifibrocyctes, just as they are after a heart attack. This opens the doors to future therapies that will be able to target specific cell types or processes in different heart diseases. This will hopefully prevent healthy cells from being permanently damaged. Persistent high blood pressure can have devastating consequences, but it is treatable, highlighting the need to monitor for high blood pressure and get it under control quickly.”
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