How blood vessels sense and react to high sugar levels
Blood vessels are essential to the proper functioning of our body. In diabetic patients, high sugar levels can make the vessels "leaky", contributing to organ malfunctions and altered healing responses. Gaining a deeper understanding of how blood vessels detect nutrient levels and translate this information into structural changes of the vessel walls could unlock a wide range of research and therapeutic opportunities.
It starts with a sugar-induced modification…
Having previously discovered that a slight modification in a protein involved in cell adhesion, β1 integrin, can modify renal cell organisation when sugar levels are chronically high, scientists from the laboratory of Prof. Bernhard Wehrle-Haller investigated and reported in their recent publication in iScience how this modification in the integrin receptor could be involved in blood vessels’ changes. Using 2D in vitro cell models, they confirmed that such a modification in the β1 integrin receptor increased the binding of an intracellular protein, which in turn led to changes in gene expression and alteration of the organisation of the blood vessel cells.
…and ends with pathological changes in the organization of blood vessel cells
As noted by the first author of the study, Dr. Adama Sidibé, these changes in gene expression and structural modifications resulted in abnormal β1 integrin localization (in orange and blue on the Figure below), which affects junctions between blood vessel cells (in purple and black), and leads to enhanced proliferation, and disorganization of the vessel wall.
These new findings shed light on the cellular mechanisms underlying the impact of diabetes and metabolic disorders on blood vessels. By elucidating the precise ways in which the metabolic changes induced by elevated sugar levels alter vascular permeability and structure, researchers uncovered critical insights that pave the way for developing therapeutic strategies aiming at normalizing abnormal blood vessels in diabetes and metabolic disorders.
On the left, an acetylation of β1 integrin induced by chronic high sugar levels favorizes abnormal cell adhesion (in light pink and blue), unstable junctions among cells (in purple and black), and uncontrolled proliferation in comparison to the right where β1 integrin is not acetylated. The inside of blood vessels corresponds to the top of the illustrations. © adapted from the graphical abstract in Sidibé et al. 2024.