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A new therapeutic target to stop cardiovascular disease in progeriated mice

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Monday, April 15, 2019

A group of researchers from the National Cardiovascular Research Centre (CNIC) and the University of Oviedo have discovered a new molecular mechanism involved in the development of early cardiovascular disease (atherosclerosis) in mice with progeria. His article, published in the prestigious journal EMBO Molecular Medicine, describes a potential therapy for this very rare genetic disease.

The Hutchinson-Gilford syndrome is a disorder that leads to premature aging of the body, which begins to become visible as soon as one is born. This deterioration leads to the appearance of atherosclerosis when individuals are still very young. People with progeria usually die between the ages of 6 and 20, mostly from myocardial infarction or stroke, both caused by atherosclerosis. The most notable physical characteristics of this disease are alopecia, thin skin, absence of subcutaneous fat, joint stiffness and fragile bones, conditions more typical of elderly people. Progeria is a laminopathy and is caused by the mutation in the LMNA gene, which codes for the protein progerin, indispensable for the stability of the nucleus of cells.

In its study, the Spanish group reveals a molecular mechanism unknown until now by which the cells of mice with progeria acquire atherosclerosis prematurely. According to the results of the study, the accelerated death of the cells of the internal wall of the blood vessels of progeric mice may be due to problems in the endoplasmic reticulum (this structure is responsible for the synthesis of proteins in the cell) and in response to poorly folded cellular proteins. The team also showed that the use of a compound called TUDCA (tauroursodeoxycholic acid) is able to inhibit the progression of vascular pathology and prolongs survival in diseased mice. 

These discoveries open the door to new lines of research on progeria and likewise shed new light on the mechanisms of cellular aging and the factors that regulate it.

Access to the original articleProgerin accelerates atherosclerosis by inducing endoplasmic reticulum stress in vascular smooth muscle cells | EMBO Molecular Medicine

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