Researchers at the Medical University of Hannover (MHH) soaked live human heart tissue in a nutrient solution and used it to test new drugs and an innovative approach to combating heart failure.

Professor Thomas Tam, director of MHH’s Institute for Molecular and Translational Therapeutic Strategies, has been researching microRNAs (miRNAs) for many years. miRNAs control inflammatory and fibrotic genes that cause stiffening of myocardial tissue (cardiac fibrosis) and, in turn, heart failure. In previous studies in cell culture and mouse models, Professor Thum has already shown that inhibition of microRNA miR-21 may have a positive effect on the development of fibrosis and therefore improve cardiac function. It’s done.

miRNAs are small RNA snippets that belong to the so-called non-coding RNAs. Although miRNAs do not contain the genetic information for producing proteins, they play important roles in controlling fundamental biological processes within cells. Therefore, they provide a new starting point for treatment.

In a new study, Professor Thum and his team have demonstrated for the first time the effectiveness of inhibiting miR-21 in human heart tissue. They used a method involving living myocardial slices (LMS).

This material comes from the MHH Clinic’s Cardiac, Thoracic, Transplant and Vascular Surgery Department and is, so to speak, tissue waste from diseased hearts that are removed as part of a transplant. These myocardial discs remain alive and beating in the nutrient solution for days and even weeks.

The results of this new collaborative research were recently european heart journal.

MicroRNA blockers ensure regression of fibrosis

Heart failure, also known in medicine as heart failure, caused the heart to no longer function properly, necessitating a transplant. When the heart is weakened by a heart attack or high blood pressure, it tries to compensate for its reduced pumping ability by increasing its own volume. The heart becomes stronger and stronger, increasingly overloaded. This very often leads to the proliferation of connective tissue cells (fibroblasts) within the heart muscle, making the heart increasingly stiff and causing fibrosis.

“miR-21 plays a crucial role in this development,” Professor Sam says. Researchers investigated what happens when miR-21’s harmful functions are turned off. To do this, they used so-called antisense molecules. This molecule binds precisely to microRNAs as a mirror image structure and is able to block microRNAs.

“We added a blocker to the culture chamber where LMS from explanted hearts damaged by fibrosis survive,” explains the cardiologist. The researchers were able to observe that the fibrosis in the tissue sections had partially regressed. As a result, the tissue became more elastic and the heart muscle cells were able to relax more during beating, improving survival.

LMS models prove their value in preclinical validation

“To our knowledge, this is the first study to directly investigate the effects of miR-21 on heart tissue in living humans,” Professor Sam says. The LMS model has proven its value in providing preclinical proof of efficacy and should also contribute to a significant reduction in animal testing in the future. “Incubation laboratory studies demonstrate that miR-21 blockers are drug candidates that have the potential to halt and even reverse the progression of fibrosis in heart failure.”

Since fibrosis can also affect other organs, antisense molecules may also be considered for the treatment of liver or lung fibrosis. “Furthermore, since heart failure is often accompanied by organ diseases such as the liver and kidneys, suppressing miR-21 could possibly also have benefits in cases of liver and kidney dysfunction,” the scientists speculated. ing.

The researchers’ next step is to figure out how to safely and precisely deliver the blockers to their intended targets. Researchers are already working on solutions that could one day deliver RNA therapeutics to different organs in a targeted manner.

Provided by Hannover Medical School