Importance of erythrocytes for endothelial metabolic activation and new vessel formation

• Applicant: Professorin Dr. Katrin Schäfer
• Subject Area: Cardiology, Angiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 555133650

Angiogenesis, the formation of new blood vessels, is an energy-consuming process, and metabolic pathways have been identified as critical regulators of blood vessel morphogenesis. First evidence suggests that erythrocytes have active roles in vascular homeostasis and disease. Based on our findings that erythrocytes enhance angiogenic sprout formation and new vessel formation by supporting endothelial cell metabolism, we plan to examine the mechanisms underlying their proangiogenic effects in more detail. Specifically, we will perform experiments to study how erythrocyte-induced changes in endothelial glycolysis, lactate generation and glutaminolysis promote angiogenic processes, including under conditions of hypoxic stress. We will focus our analyses on the metabolic regulation of the transcription factor hypoxia-inducible factor-1 alpha (HIF-1α) as key signalling hub controlling endothelial gene expression and function to promote angiogenesis (WP1). In addition to acute effects of erythrocytes on endothelial metabolism, we will study the horizontal transfer of erythrocyte proteins and their uptake by endothelial cells as a mechanism of erythrocyte–endothelial cell communication during new vessel formation (WP2). We also will study the role of glycolytic enzymes expressed in the erythrocyte membrane and their regulation by phosphorylation of the anion exchanger band 3 (WP3). Based on our observations that erythrocytes from patients with peripheral artery disease do not promote angiogenesis, we also will explore the contribution of erythrocyte dysfunction to impaired vascularisation and differentiate it from endothelial dysfunction (WP4). We expect that our studies will provide novel insights into the role of erythrocytes in supporting endothelial metabolic adaptions during angiogenesis and how these functions are altered in patients with impaired neovascularisation as seen in peripheral artery disease.

• DFG Programme: Research Grants