Groundbreaking research on angiogenesis reveals how blood vessels communicate through metabolic signals
Every tissue and organ in our body is nourished by an exquisite network of blood vessels that extends over 60,000 miles—a length that could circle the Earth twice.
Professor Michael Potente's groundbreaking research has been honored with the prestigious 2023 Judah Folkman Award 2 .
"By looking at how endothelial cells sense and use metabolic signals, we want to identify regulatory principles and find out how perturbations in them promote disease." - Michael Potente 2
Blood vessels are dynamic, living tissues that actively communicate with the organs they serve. The inner lining of these vessels—the endothelium—consists of a single layer of extraordinary cells that constantly sense environmental changes 2 .
Endothelial cell functions in vascular regulation
Endothelial cells detect metabolic needs from surrounding tissues
Cells release signaling molecules in response to tissue demands
New connections form to meet increased nutrient requirements
One of Potente's most significant contributions has been identifying YAP and TAZ proteins as master regulators of blood vessel growth 6 .
"Together, we've discovered a mechanism that enables blood vessels to align their growth closely to the situation in their surroundings," said Holger Gerhardt 6 .
Potente's team uncovered a remarkable system that maintains endothelial cells in their quiet, resting state .
| Experimental Component | Finding | Significance |
|---|---|---|
| FOXO1 activation | Increased S-2-HG production | Identified a novel metabolic regulator |
| S-2-HG application to endothelial cells | Induced quiescence | Demonstrated sufficiency of the metabolite |
| S-2-HG removal | Restored angiogenic capacity | Showed reversible effect |
| In vivo mouse models | Prevented pathological angiogenesis | Confirmed physiological relevance |
Complete signaling pathway identified by Potente's team
The implications of this experiment are profound. The research team had identified a complete signaling pathway that represents a fundamental biological mechanism maintaining vascular stability .
| Condition | Vascular Problem | Potential Therapeutic Approach |
|---|---|---|
| Cancer | Excessive vessel growth feeding tumors | Enhance FOXO1/S-2-HG pathway to calm vessels |
| Coronary artery disease | Insufficient vessel growth around blockages | Temporarily inhibit FOXO1/S-2-HG to promote growth |
| Diabetic retinopathy | Abnormal vessel growth in the retina | Activate calming pathway to prevent leakage |
| Chronic wounds | Inadequate vessel regeneration | Modulate pathway to enable controlled growth |
"This variant differs in structure and function from the metabolite produced in some cancer cells," noted Ana Costa .
"Our long-term goal is to be able to therapeutically influence the development and function of blood vessels in a targeted manner, and if possible, without any side effects," Potente explained .
Potente's discoveries have been enabled by sophisticated research technologies that allow precise examination of vascular biology 4 .
| Reagent/Technology | Function | Application in Potente's Research |
|---|---|---|
| Genetically modified mouse lines | Enable study of specific genes in vivo | Demonstrated necessity of YAP/TAZ for vessel growth 6 |
| Small interfering RNA (siRNA) | Temporarily suppresses specific genes | Used to study individual HDAC isoenzymes in angiogenesis 9 |
| Ultra-high performance liquid chromatography | Precisely measures metabolite levels | Quantified ImP levels in human patients 8 |
| Tamoxifen-inducible Cre-loxP system | Allows timed gene activation/inactivation | Studied endothelial FOXO1 signaling in mice 8 |
| Next-generation sequencing | Reveals comprehensive genetic information | Investigated molecular mechanisms of metabolite action 8 |
| Chromatin immunoprecipitation | Identifies where transcription factors bind | Showed HDAC5 binding to FGF2 and Slit2 promoters 9 |
Michael Potente's research has fundamentally expanded our understanding of how blood vessels grow, remain stable, and malfunction in disease.
Revealed the communication between metabolism and angiogenesis 6 .
Findings offer promise for precise modulation of blood vessel growth 2 .
Potential to improve treatments for cancer, diabetes, and cardiovascular diseases.
In a field where there is truly "no time to waste," Michael Potente's research is lighting the path toward more effective vascular therapies that could improve millions of lives.