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 investigation, started in 2012, were published in the scientific magazine 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 from cardiovascular disease, around 14 years of age.
This disease, explains Patrícia Pitrez, 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 observed in normal aging, albeit to a lesser extent».
“As this project is related to pathological vascular aging (progeria), the knowledge generated is also of great importance in physiological vascular aging”, he stresses.
The study focused on smooth muscle cells (cells found in blood vessels), as they are the 'most affected cells in progeria', with a decrease in their number in aging arteries. But the reason for this loss was not yet known. We collect skin cells (fibroblasts) from individuals with and without progeria, reprogrammed into stem cells and then differentiated 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, reports Patrícia Pitrez, it was possible to “maintain the cells in conditions of arterial flow, very similar to the conditions existing in 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 understand why the number of cells decreased 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 about 30-fold increased in progeria smooth muscle cells compared to with the 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 counteract the decrease in the number of cells in 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 the quality and average life expectancy of these individuals'. On the other hand, they conclude, the microchip developed within the scope of this research «it 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 Programme, and ERAatUC – and Portuguese funds, 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), Molecular Genetics Laboratory (France) participated in the research. , Francis Crick Institute (UK), University of Liverpool (UK), Leibniz Institute of Aging (Germany), AFM Telethon (France) and Cambridge Science Park (UK).
Author: Cristina Pinto – Press Office – University of Coimbra – Science Communication
Science in the Regional Press – Ciência Viva
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