![[Translate to English:] Mikroskopische Bilder, die ein komplexes Netzwerk aus roten, aderartigen Strukturen mit verstreuten cyanfarbenen Punkten vor einem dunklen Hintergrund zeigen.](/fileadmin/_processed_/3/d/csm_cystin_0316ab0b5e.jpg)
Cardiovascular diseases such as heart attacks, strokes, diabetes and high blood pressure are the most common causes of death in Germany. Blood vessels play a key role in the development of these and other diseases. In particular, the endothelial cells lining the vessels are of central importance to human health as so-called gatekeepers. Endothelial metabolism is the basis for tissue regeneration, health and longevity.
The Department of Vascular Dysfunction at Heidelberg University's Mannheim Medical Faculty, headed by Professor Sofia-Iris Bibli (DZHK scientist), is researching the molecular mechanisms that control the growth, regeneration, regression and ageing of blood and lymph vessels. In their current work, the scientists have identified a previously unknown oxidative metabolic pathway in the cell nucleus through which epithelial cells control vascular growth. It links cystine to epigenetic gene regulation and opens up new therapeutic perspectives for the repair of vascular damage. The work has been published in the renowned journal Cell Metabolism.
Cystine consists of two molecules of the sulphur-containing amino acid cysteine, which are linked by a disulphide bond. It is found in many protein-rich foods, including grains, nuts, meat, fish, dairy products and eggs. In their study, the scientists show that cystine supplied through food is oxidatively degraded in the cell nucleus and is crucial for vascular growth and the regeneration of damaged vessels, even though cysteine is a non-essential amino acid because it can be synthesised by the body itself.
However, this newly identified nutrient-dependent control mechanism declines with age. But it can be revived: targeted supplementation with cystine restores vascular growth in cases of injury, disease and ageing. Cystine supplementation promotes vascular repair in retinopathy of prematurity, after myocardial infarction and in cases of injury in old age.
‘We have shown that endothelial cells determine how they will adjust their nutrient uptake and utilisation even before active proliferation begins,’ says Sofia-Iris Bibli. ‘The therapeutic effects confirm the role of oxidative cystine catabolism in the cell nucleus as a fundamental metabolic axis linking nutrient utilisation and gene regulation – with extensive implications for vascular regeneration.’
The scientists were able to elucidate the epigenetic mechanism: endothelial cells preparing for proliferation actively control cystine import into the cell via a so-called solute carrier (SLC) transporter. There, cystine forms a complex with cystathionine gamma lyase (CSE) and pyruvate dehydrogenase and is oxidatively degraded in the cell nucleus by CSE. It was shown that cystine itself, via oxidative degradation to pyruvate, drives the production of acetyl groups in the cell nucleus that specifically acetylate histone H3. This loosens the chromatin structure and makes it accessible to endothelial transcription, leading to proliferation and vascular growth.
The study included a clinical cohort, several in vivo mouse models, cell culture approaches with targeted gene modulation, and extensive functional vascular analyses.
Original publication: Drekolia et al., Cystine import and oxidative catabolism fuel vascular growth and repair via nutrient-responsive histone acetylation, Cell Metabolism (2025)
Source: Press release University Medical Centre Mannheim
