DZHK Junior Research Groups - Stress management in the heart
- Project leader: Dr. Alexander Bartelt
- Affiliation: Institute of Cardiovascular Prevention (IPEK)
- Funding: 2018 to 2023
When the heart gets into stress, for example through rhythm disturbances or atherosclerosis, a molecular emergency plan comes into effect that modifies the metabolism of the heart muscle cells and is supposed to maintain the correct function of the organ. Alexander Bartelt's goal is to decipher the mechanisms of this stress reaction and transfer research results into clinical practice. The biochemist and molecular biologist has previously carried out research at Harvard University (USA) and is now setting up a new junior research group at the Institute for the Prevention and Epidemiology of Cardiovascular Diseases (IPEK) headed by Professor Christian Weber. Over the next five years, the group will receive 1.25 million euros in funding from the German Centre for Cardiovascular Research (DZHK).
The most important cell organelle involved in the adaptation of the metabolism is the endoplasmic reticulum (ER), an extensive network of membrane channels. Among other things, it is responsible for the production and correct folding of proteins and plays an important role in fat metabolism. If the heart is exposed to stress, for example as a result of a heart attack, it has to adapt quickly and effectively in order to ensure its function and survival. ER can protect cells from toxic effects and ensure that defective or harmful proteins are degraded and disposed of. This degradation takes place in the proteasome, a large complex that functions as a protein shredder. "We are particularly interested in the role of the transcription factor Nfe2l1, which is located in the ER and controls the activity of the proteasome," said Bartelt.
In a study recently published in the renowned journal Nature Medicine, Bartelt was able to show that so-called brown fat cells, which can produce heat through the oxidation of fatty acids, modify their metabolism with the help of the proteasome - and that Nfe2l1 is a key factor that protects the cells against metabolic stress. "The Nfe2l1 proteasome mechanism is also very active in the heart," said Bartelt. "We therefore assume that Nfe2l1 plays an important role in the protection against heart diseases. Using cell cultures and specific animal models, the researchers now hope to investigate the biological importance of Nfe2l1 and the proteasome at the molecular level. Together with clinical partners in the Munich Heart Alliance, the scientists want to extend their research results to humans in order to open up new treatment options for cardiovascular diseases.