Spatiotemporal atlas of vascular inflammaging and therapeutic targeting of DPP4 for endothelial resilience – SVITER
Could a Diabetes Drug Help Slow Vascular Aging?
An existing class of diabetes medications may hold unexpected promise for protecting blood vessels as we age.
The connection to DPP4
DPP4 is a protein found on the surface of blood vessel cells (endothelial cells) and immune cells. Its job is to regulate a wide range of inflammatory substances in the body — including various interleukins, growth factors, and cytokines — by trimming them at one end. Because of this broad reach, the research group located in the Department of Anesthesiology postulates DPP4 acts as a kind of master switch for inflammatory signaling. Their previous research has shown that DPP4 inhibition can calm down several inflammatory pathways, including ones involved in blood vessel cell activation and immune system overactivation.
DPP4 inhibitors, commonly known as “gliptins,” are already approved and widely used as diabetes drugs, since they also affect blood sugar regulation. They’re water-soluble, generally well-tolerated, and have a strong safety track record.
Beyond diabetes, evidence is growing that DPP4 plays a role in vascular aging itself. Blocking DPP4 has been shown to reduce cell aging (senescence) in blood vessels, lower oxidative stress, prevent stress-related vascular aging, and help restore the body’s supply of vascular repair cells. In obese patients, this same pathway appears to drive blood vessel aging — and blocking DPP4 improved vessel function in lab studies. Teamed up with specialists in bioinformatics from the Department of Dermatology, the team will evaluate the exciting possibility: an already-approved, safe medication could potentially be repurposed to protect aging blood vessels.
Early findings from this research group
Prior work by the team found that giving a DPP4 inhibitor (sitagliptin) to surgical patients , who experience a temporary, intense inflammatory response during major surgery, helped protect their small blood vessels from inflammation-related dysfunction. Similar protective effects were seen in mouse studies, where DPP4 inhibition (or genetically removing DPP4 altogether) reduced inflammation-induced blood vessel problems. The team has also successfully identified and tracked distinct subtypes of blood vessel cells in the brain and shown that these subtypes respond differently to inflammation. The project lays important groundwork for more detailed studies.
What this research aims to do next
Building on these findings, the project has three main goals:
Map how blood vessels age — creating a detailed and integrated single cell atlas of how vessel-lining cells change over time across 11 different tissues and different types of blood vessels.
Connect these changes to real outcomes — linking age-related cellular changes to actual measures of vascular and organ health.
Test DPP4 as a treatment target — determining exactly how important DPP4 is in protecting blood vessels during aging, and whether DPP4 inhibitor drugs could become a new strategy to slow age-related vascular decline.
Principle Investigators
· Dr. Maximilian Sprang Department of Dermatology, University Medicine Mainz (person of contact email)
· Dr. Miriam Julia Renz, Department of Anesthesiology, University Medicine Mainz
