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Research Group Schwedhelm
Aim:
We aim to understand the role of distinct mediators of cardio- and cerebrovascular disease, i.e. sphingosin-1-phosphate or homoarginine.
Scope of Research
arterial injury mouse model • clinical trials and cohort studies • mass spectrometry • stroke mouse model
Research Projects
1. The sphingolipid sphingosin-1-phosphate (S1P) is involved in the regulation of pathophysiologic changes underlying atherosclerosis such as intimal hyperplasia, but also neurodegenerative and -inflammatory diseases. We investigate which of the S1P receptors contribute and if pharmacological intervention can modulate the progression of vascular (re)stenosis. Furthermore, S1P receptor agonists like fingolimod confer neuroprotective effects in cell and mouse models of stroke, multiple sclerosis, and Parkinson’s disease.
2. Nitric oxide (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.
Key Techniques
- arterial injury mouse model, mass spectrometry, stroke mouse model
- mass spectrometry, stroke mouse model
Group Members
Publications
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Association of asymmetric and symmetric dimethylarginine with inflammation in the population-based study of health in Pomerania.
Winkler MS, Bahls M, Böger RH, Ittermann T, Dörr M, Friedrich N, Schwedhelm E (2023).
Biomolecules. 13:1612. doi: 10.3390/biom13111612
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Effective high-density lipoprotein cholesterol is associated with carotid intima-media thickness and vascular events after acute ischemic stroke.
Schwedhelm E*, Tiedt S*, Lezius S, Wölfer TA, Jensen M, Schulz R, Böger R, Gerloff C, Thomalla G, Choe CU (2022).
Atherosclerosis. 357:9-13. doi: 10.1016/j.atherosclerosis.2022.08.001
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Expression of cardiovascular-related microRNAs is altered in L-arginine:glycine amidinotransferase deficient mice.
Jensen M, Müller C, Hübner N, Patone G, Saar K, Choe CU, Schwedhelm E, Zeller T (2022).
Sci Rep. 12:5108. doi: 10.1038/s41598-022-08846-1
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Serum sphingosine-1-phosphate levels are associated with severity and outcome in patients with cerebral ischemia.
Schwedhelm E*, Schwieren L*, Tiedt S, von Lucadou M, Gloyer N, Böger R, Magnus T, Daum G, Thomalla G, Gerloff C, Choe CU (2021).
Stroke. 52:3901-3907. doi: 10.1161/STROKEAHA.120.033414
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Arginine:glycine amidinotransferase is essential for creatine supply in mice during chronic hypoxia.
Hannemann J, Cordts K, Seniuk A, Choe CU, Schmidt-Hutten L, Duque Escobar J, Weinberger F, Böger R, Schwedhelm E (2021).
Front Physiol. 12:703069. doi: 10.3389/fphys.2021.703069
Grants/Awards
- DZHK e.V. Standortprojekt
Most important collaboration partners
- Vasan Ramachandran, UT School of Public Health, San Antonio
- Craig Lygate, School of Cardiovascular & Metabolic Health, Glasgow