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International team led by UC discovers protein associated with vascular aging

An international team coordinated by scientist Lino Ferreira, from the Faculty of Medicine of the University of Coimbra (FMUC) and the Center for Neuroscience and Cell Biology (CNC-UC), discovered an enzyme (protein) that is involved in diseases related to vascular aging.

The results of the research, which began in 2012, were published today in the scientific journal Nature Communications and may contribute to the development of new drugs to combat diseases associated with premature aging and physiological aging.

In this project, cells from individuals with Hutchinson-Gilford Syndrome or Progeria were used, a very rare disease, characterized by premature aging and premature death, usually due to cardiovascular disease, around 14 years of age.

This disease, explains Patrícia Pitrez, the first author of the scientific article now published, “is caused by a rare genetic mutation in the LMNA gene, which results in the accumulation of an abnormal protein inside cells, called progerin. This protein is also seen in normal aging, albeit on a smaller scale”.

“As this project is related to pathological vascular aging (progeria), the knowledge generated is also of great importance in physiological vascular aging”

“The study focused on smooth muscle cells (cells found in blood vessels), since they are the cells’ most affected in progeria, with a decrease in their number in aged arteries. But the reason for this loss was not yet known. We collected skin cells (fibroblasts) from individuals with and without progeria, reprogrammed them in stem cells and then differentiated them into smooth muscle cells”, clarifies the CNC researcher.

 

Then, to assess the mechanisms involved in vascular biology, the team developed two vascular microchips – one healthy and one aged (progeria).

In these devices, Patrícia Pitrez reports, it was possible “to keep the cells in conditions of arterial flow, very similar to the conditions existing in the arteries, and this allowed us to study the susceptibility of these progeria cells in the laboratory.

After a few days we noticed a decrease in the number of progeria smooth muscle cells, but not healthy ones. And through this system, it was possible to analyze the differences between the two microchips, that is, to compare the two types of cells and to understand the reason for the decrease in the number of cells in the case of progeria”.

And it was precisely in the process of analyzing the differences between healthy and progeria cells that the researchers discovered “an enzyme, metalloproteinase 13 (MMP13), whose concentration is approximately 30 times increased in progeria smooth muscle cells in comparison with healthy ones”, he stresses.

In an attempt to inhibit the action of this enzyme, the researchers also tested a drug, having managed to develop a specific therapy to counter the decrease in the number of cells in the arteries that occurs with vascular aging.

In view of the results obtained, the study authors believe “that the administration of the drug in the early stages of the disease, combined with other drugs already tested and that reduce the amount of progerin, can be of added value to improve quality and average life expectancy these individuals”.

On the other hand, they conclude, the microchip developed in the scope of this research “also opens new perspectives for the development of other treatments, not only for individuals with progeria, but also for physiological vascular aging”.

The project was co-financed by European funds – FEDER, through the COMPETE Program, and ERAatUC – and Portuguese, through the Foundation for Science and Technology (FCT).

In addition to the University of Coimbra, scientists from the Institute of Molecular Medicine (Portugal), I-Stem (France), University of Aix-Marseille (France), Autonomous University of Barcelona (Spain), Laboratory of Molecular Genetics (France), Francis Crick Institute (United Kingdom), University of Liverpool (United Kingdom), Leibniz Institute for Aging (Germany), AFM Telethon (France) and Cambridge Science Park (United Kingdom).

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