Research Focus and Main research questions
Function and integrity of the vasculature is controlled by diverse mediators. Our research interest focusses on sphingosin-1-phosphate (S1P) and the vasodilator nitric oxide (NO). The sphingolipid S1P is involved in the regulation of pathophysiologic changes underlying atherosclerosis such as intimal hyperplasia, but also neurodegenerative diseases. We investigate which of the S1P receptors contribute and if pharmacological intervention can modulate the progression of intimal hyperplasia and vascular restenosis. Furthermore, S1P receptor agonists like fingolimod confer neuroprotective effects in cell and mouse models of stroke, multiple sclerosis, and Parkinson’s disease. On the other hand, NO biosynthesis can be impaired by endogenous L-arginine derivatives, i.e. asymmetric dimethylarginine (ADMA) or symmetric dimethylarginine (SDMA). Investigations revealed that genetically modified mice lacking the ADMA-degrading enzyme dimethylarginine dimethylamine hydrolase (DDAH) are suffering from high blood pressure and endothelial dysfunction.
In contrast, the naturally occurring amino acid homoarginine is protective in cardio- and neurovascular disease. In line with clinical data, disruption of the homoarginine generating enzyme L-arginine:glycine-amidinotransferase (AGAT) in mice results in different cardio- and neurovascular phenotypes, which can be resolved upon homoarginine-supplementation