Our study demonstrated that human blood vessel organoids are promising tissue models for human biology and disease that can bridge the gap between preclinical platforms and clinical trials. This model can be utilised for mechanistic studies and the identification of potential targets for novel therapeutic approaches.”
Dr Anna Zampetaki, Lecturer in Cardiovascular Biology
18 October 2023
Metabolism plays key role in delivering nutrients to body's cells
A new paper highlights how the blood vessels that give cells oxygen and nutrients are affected by metabolic changes, which could help tackle ageing and cardiovascular diseases.
The microvasculature refers to the small vessels that control the exchange of oxygen and nutrients from the bloodstream to individual cells. These structures are found throughout the body and their impairment is considered a key characteristic of ageing, as well as cardiovascular diseases.
An important measure of microvascular stability is the interaction of the two main vascular cells in the microvessels, the pericytes (PC) and the endothelial cells (EC). However, little is known about the mechanism that underpin these interactions.
In the study published in Nature Communications, the researchers explain how they used human blood vessel organoids (BVOs) as a model of the microvasculature and tested these interactions as they occur in human tissue. Aiming to understand how the microvasculature senses and responds to metabolic changes, the study inhibited glycolysis – the process that breaks down glucose to generate energy for cells.
The researchers found that inhibition induced a rapid remodelling of the structure, observing a reduction in length and density of the vessels in the microvasculature and an increase in its instability.
Inhibition was also found to drive the suppression of an important pathway within the cell that produces a molecule called CTGF. When this molecule was supplemented, the damaging structural remodelling was prevented and PC:EC interactions were restored.
These results show that CTGF plays an important role in maintaining the microvasculature structure. Targeting this molecule could be a potential therapeutic strategy to counter instability in the microvasculature.
The success of the study also suggests that human BVOs have potential as an experimental model within human biology. In particular, the authors highlight how the short timeframe of response from human BVOs is well-suited for efficiently screening potential drugs when testing for new therapies.
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School Lead DDI