Nav: Home

A new therapeutic target for blocking early atherosclerosis in progeria

March 12, 2019

Researchers at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) and the Universidad de Oviedo have discovered a new molecular mechanism involved in the premature development of atherosclerosis in mice with Hutchinson-Gilford progeria syndrome (HGPS). Moreover, the results, published in EMBO Molecular Medicine, identify a potential therapeutic target for this severe genetic disease, which is characterized by the premature onset of cardiovascular disease and early death, usually from a heart attack or stroke, between the ages of 6 and 20 years.

Progeria is very rare genetic disease caused by a mutation in the LMNA gene. The disease affects an estimated 400 people worldwide. HGPS patients show accelerated aging linked to a high risk of cardiovascular disease. In the words of study leader Vicente Andrés, studying this disease "brings us closer to a possible treatment for disease victims and can provide important information about normal physiological aging and the factors that regulate it."

Atherosclerosis is a degenerative disease in which cholesterol and immune cells accumulate in the blood vessel walls, forming plaques or plugs that obstruct blood flow. Rupture of atherosclerotic plaques can trigger a life threatening myocardial infarction or stroke. Many of the factors that increase the risk of atherosclerotic cardiovascular disease can be controlled by changes to lifestyle, including a healthy diet, physical activity, and stopping smoking, as well as medical treatment. However, the main risk factor is aging, which cannot be modified. This situation is aggravated in progeria patients, whose arteries have multiple defects, including loss of smooth muscle cells and the formation of atherosclerotic plaques.

Molecular mechanism

The new study was co-directed by Vicente Andrés of the CNIC and the Centro de Investigación en Red en Enfermedades Cardiovasculares (CIBERCV) and Carlos López Otín of the Universidad de Oviedo. The study identifies a molecular mechanism involved in the accelerated development of atherosclerosis in progeria. In addition, the results suggest a possible pharmacological treatment that slows the progression of atherosclerosis and extends the lifespan of progeroid mice.

Little is known about the mechanisms underlying early vascular disease in progeria because there are so few patients and because animal models of this disease have not developed atherosclerosis. Vicente Andrés' group recently generated the first mouse model that recapitulates the accelerated atherosclerosis in HGPS induced by the protein progerin. The results of the analysis of these mice, published in 2018 in Circulation, identified vascular smooth muscle cells as a possible target for the treatment of premature atherosclerosis in progeria.

Tauroursodeoxycholic acid

The EMBO Molecular Medicine study, featured in an editorial in the journal, shows for the first time that "stress in the endoplasmic reticulum (ER stress) and the associated unfolded protein response (UPR) are involved in the death of vascular smooth muscle cells in progeroid mice," explains first author Magda Hamczyk. "We therefore think that treatments targeting these cellular stress pathways could be effective against vascular disease in progeria."

The research team used the compound tauroursodeoxycholic acid (TUDCA), which reduces the negative consequences of the activation of the ER stress and UPR pathways. According to Vicente Andrés, "treatment of progeroid mice with TUDCA inhibits the progression of vascular disease, including vascular smooth cell loss and atherosclerosis. TUDCA also prolonged the lifespan of progeroid mice, which die from the complications of atherosclerosis".

The authors conclude that "these findings open a new research avenue in progeria and suggest that TUDCA could be used to treat vascular disease in HGPS patients and extend their life expectancy."
-end-


Centro Nacional de Investigaciones Cardiovasculares Carlos III (F.S.P.)

Related Stress Articles:

How stress remodels the brain
Stress restructures the brain by halting the production of crucial ion channel proteins, according to research in mice recently published in JNeurosci.
Why stress doesn't always cause depression
Rats susceptible to anhedonia, a core symptom of depression, possess more serotonin neurons after being exposed to chronic stress, but the effect can be reversed through amygdala activation, according to new research in JNeurosci.
How plants handle stress
Plants get stressed too. Drought or too much salt disrupt their physiology.
Stress in the powerhouse of the cell
University of Freiburg researchers discover a new principle -- how cells protect themselves from mitochondrial defects.
Measuring stress around cells
Tissues and organs in the human body are shaped through forces generated by cells, that push and pull, to ''sculpt'' biological structures.
Cellular stress at the movies
For the first time, biological imaging experts have used a custom fluorescence microscope and a novel antibody tagging tool to watch living cells undergoing stress.
Maternal stress at conception linked to children's stress response at age 11
A new study published in the Journal of Developmental Origins of Health and Disease finds that mothers' stress levels at the moment they conceive their children are linked to the way children respond to life challenges at age 11.
A new way to see stress -- using supercomputers
Supercomputer simulations show that at the atomic level, material stress doesn't behave symmetrically.
Beware of evening stress
Stressful events in the evening release less of the body's stress hormones than those that happen in the morning, suggesting possible vulnerability to stress in the evening.
How plants cope with stress
With climate change comes drought, and with drought comes higher salt concentrations in the soil.
More Stress News and Stress Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Teaching For Better Humans 2.0
More than test scores or good grades–what do kids need for the future? This hour, TED speakers explore how to help children grow into better humans, both during and after this time of crisis. Guests include educators Richard Culatta and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

Space
One of the most consistent questions we get at the show is from parents who want to know which episodes are kid-friendly and which aren't. So today, we're releasing a separate feed, Radiolab for Kids. To kick it off, we're rerunning an all-time favorite episode: Space. In the 60's, space exploration was an American obsession. This hour, we chart the path from romance to increasing cynicism. We begin with Ann Druyan, widow of Carl Sagan, with a story about the Voyager expedition, true love, and a golden record that travels through space. And astrophysicist Neil de Grasse Tyson explains the Coepernican Principle, and just how insignificant we are. Support Radiolab today at Radiolab.org/donate.