MedUni Vienna: Cardiac sarcoidosis identifies enzyme as a target for combating scarring of the heart
A research team led by the Medical University of Vienna has discovered a new mechanism that drives scarring of the heart in sarcoidosis. At the centre of this is the enzyme MMP12, which is released by immune cells in inflamed tissue. The findings, recently published in the American Journal of Respiratory and Critical Care Medicine, could pave the way for new treatment strategies in the long term.
Sarcoidosis is an inflammatory disease in which nodular tissue, known as granulomas, can develop in various organs. In Austria alone, several thousand people are estimated to be affected. Around five per cent have clinically detectable cardiac involvement, although autopsy and imaging studies suggest signs of heart involvement in up to one quarter of patients. As a result, cardiac sarcoidosis often remains undetected despite its potential to cause severe cardiac arrhythmias, heart failure and sudden cardiac death. A particular challenge is the progressive scarring of heart tissue (fibrosis), for which only limited treatment options are currently available.
The team led by Thomas Weichhart from the Center for Pathobiochemistry and Genetics at MedUni Vienna has now shown that a specific group of immune cells, macrophages, plays a central role in the development of cardiac fibrosis in sarcoidosis. The researchers identified the protein MMP12 as the key driver. This enzyme breaks down components of connective tissue and initiates a remodelling process that ultimately leads to increased scar tissue formation. Importantly, elevated MMP12 activity was demonstrated not only in a preclinical animal model but also in heart tissue from patients with cardiac sarcoidosis.
“What was particularly remarkable for us was that the same immune cells that initially form the granuloma also later drive the scarring of the heart,” explains first author Mario Mazic. “This allowed us to identify, for the first time in cardiac sarcoidosis, a mechanism linking these two disease processes.”
The study also showed that blocking MMP12 in the animal model significantly reduced inflammation, granuloma formation and cardiac scarring. The MMP12 inhibitors used in the study had already been developed for other chronic inflammatory diseases and are currently being further developed by the pharmaceutical company Foresee Pharmaceutical as a potential treatment for cardiac sarcoidosis. Parts of the study were supported by an unrestricted research grant from Foresee Pharmaceutical.
“For patients, the most important aspect is that we have not only identified a new disease mechanism but also a concrete therapeutic target,” says study leader Thomas Weichhart. “Since suitable MMP12 inhibitors are already available, there is now an opportunity to evaluate these findings comparatively quickly in a clinical trial.”
Before such a therapeutic approach can be used in patients, further clinical studies will be required. Nevertheless, the current findings provide an important foundation for the development of new therapies for cardiac sarcoidosis.