The enzyme tubulin tyrosine ligase (TTL) plays a crucial role in regulating the stability of microtubules - part of the cell's cytoskeleton - which are responsible for cells' structural integrity and mechanical stability. TTL adds a tyrosine amino acid to tubulin proteins (tyrosination), affecting the flexibility of the microtubules and how cells respond to mechanical stress. This is especially important in heart muscle cells, where it supports contraction and the heart’s adaptation to pressure.
Reduced Myocardial Stiffness After 12 Weeks
In a series of experiments, the research team demonstrated that overexpression of TTL significantly improved heart function. In mouse models, after twelve weeks, the heart muscle cells showed reduced stiffness and improved contractility.
Human heart muscle cells derived from stem cells of HCM patients also showed normalized cell size. These positive effects suggest a potential future therapy that could improve heart function without invasive procedures.
Hope for New Treatment Options
For approximately 160,000 persons affected by HCM in Germany, these findings offer hope for a new treatment option. This method could complement conventional medications or surgeries, improving patients' quality of life by stabilizing heart function and slowing disease progression. This could be especially important for those with severe symptoms, such as reduced heart performance or heart failure.
“Our results indicate that modulating the cytoskeleton through tubulin tyrosination offers a promising therapeutic strategy to improve heart function in genetic heart diseases like HCM.” says Prof. Dr. Lucie Carrier, the project’s lead scientist, Insitute of Experimental Pharmacology and Toxicology at the University Hospital Hamburg-Eppendorf.
Original publication:
Chronic Activation of Tubulin Tyrosination Improves Heart Function. Pietsch, N. et al., Circulation Research, 2024
Scientific contact:
Prof. Dr Lucie Carrier (l.carrier@uke.de), Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Center, UKE
