Cardiovascular diseases remain the most common cause of death worldwide. In Europe, they account for over 40 percent of all deaths. However, known risk factors such as high cholesterol levels or high blood pressure cannot fully explain the high mortality rate or the number of cardiovascular diseases. Scientists in Graz have now investigated a new factor that is closely linked to cardiovascular mortality. Elevated levels of the amino acid homocysteine in the blood led to a stiffer and less elastic aorta in an animal model. These findings contribute to the current understanding of the development of cardiovascular diseases such as atherosclerosis, in which the role of cholesterol has previously been more in focus.
Focus on the aorta
The aorta is the largest blood vessel in the human body. With each heartbeat, it must contract and expand to transport oxygen-rich blood from the heart to the organs. "Many cardiovascular diseases have their origin in aortic dysfunction," explains Gerhard A. Holzapfel from the Institute of Biomechanics at Graz University of Technology (TU Graz). Together with Francesca Bogoni (TU Graz) and Oksana Tehlivets from the Institute of Molecular Biosciences (University of Graz), he is conducting research on the mechanical properties of the aorta.
In a recent publication, the scientists, together with partners from the Medical University of Graz, investigated the effects of homocysteine on the aorta. This "cell poison" is produced as an intermediate product during the metabolism of another amino acid, methionine. "If it is not broken down quickly, homocysteine accumulates. This is often observed in older people. A high-fat diet and lack of exercise may also contribute to an increase in homocysteine levels in the blood," explains Oksana Tehlivets.
Too much homocysteine makes the aorta stiff
The researchers focused their studies on the role of this amino acid. "We deliberately left out the influence of cholesterol, as we already know that too much of it thickens the blood vessels. However, the fact that elevated homocysteine levels make blood vessels stiffer and less elastic was previously less recognized as a risk factor," explains Francesca Bogoni.
The research findings lay the foundation for a better understanding of the mechanisms that cause atherosclerosis and cardiovascular disease in general. The research was funded by the Austrian Science Fund (FWF) and BioTechMed-Graz, the joint health research network of the University of Graz, the Medical University of Graz and the Graz University of Technology.
Publications:
Bogoni et al. Homocysteine leads to aortic stiffening in a rabbit model of atherosclerosis. Acta Biomaterialia, 2025. DOI: https://doi.org/10.1016/j.actbio.2025.06.003
Tehlivets et al. Homocysteine contributes to atherogenic transformation of the aorta in rabbits in the absence of hypercholesterolemia. Biomedicine & Pharmacotherapy, 2024.
DOI: https://doi.org/10.1016/j.biopha.2024.117244
Bogoni et al. On the experimental identification of equilibrium relations and the separation of inelastic effects of soft biological tissues. Journal of the Mechanics and Physics of Solids, 2024.
DOI: https://doi.org/10.1016/j.jmps.2024.105868
