Above: The proepicardium is a layer of cells that form the epicardium that surrounds the heart.
A major problem for heart attack patients is that their hearts might not recover properly. With the human heart’s limited potential for regeneration and repair, a large portion of lost cardiac tissue from a heart attack is replaced by stiff fibrotic tissue. This leads to a progressive decrease in heart function and eventually heart failure.
In a recent study published in The Journal of Clinical Investigation (JCI), Dr. Manvendra Singh (Duke-NUS) and Drs. Jonathan Epstein and Rajan Jain (Penn) discovered how a signalling pathway, called Hippo, controls fibrotic tissue or scar formations after a heart attack.
This discovery may lead to the development of new drugs to treat heart failure patients by inhibiting the formation of excessive fibrotic tissue in order to preserve heart function.
In the study, the scientists determined the functions of the Hippo signaling pathway in the adult mouse epicardium, a tissue known to contribute to cardiac fibrosis after myocardial injury, by genetically deleting Hippo signaling proteins YAP and TAZ.
(Left) The loss of the proteins in the epicardium resulted in increased inflammation, formation of more fibrotic tissue, cardiomyopathy (disease of the heart), and death after heart failure. They were able to show that YAP and TAZ were the factors that provided an immunosuppressive response that protected the heart during the recovery process following a heart attack.
“It will be interesting to see whether this pathway could be pharmacologically targeted to inhibit fibrosis and to improve cardiac function after heart attack,” said Dr. Singh, who in 2015, was awarded the NRF Fellowship by the National Research Foundation in Singapore to do translational research in the field of cardiovascular medicine.
Dr. Singh hopes to extend this work and collaborate with researchers in Singapore to bring a viable treatment to the clinic.
About the Scientist
In 2014, Assistant Professor Manvendra Singh joined Duke-NUS Medical School (Duke-NUS)’s Cardiovascular and Metabolic Disorders Programme with a wealth of experience in cardiovascular research that he had built in the Perelman School of Medicine at the University of Pennsylvania (Penn). During his training at Penn, he had worked to better understand congenital and adult cardiac diseases including myocardial infarction, or heart attacks.