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The Spanish researcher’s team Ana Maria Ravenof the Albert Einstein College of Medicine (USA), has discovered that accelerating a process that slows down as we age can protect against atherosclerosis, one of the main causes of heart attacks and strokes.
Their results, published in “Proceedings of the National Academy of Sciences” (PNAS), show that this therapy, which consists of promoting this process, called chaperone-mediated autophagyreduced plaque that narrows arteries in mice.
Chaperone-mediated autophagy is a cell cleaning process that Dr. Cuervo discovered in 1993 and named in 2000.
“We have shown that we need this process to protect ourselves againstto atherosclerosiswhich progresses when this autophagy decreases, something that also happens when people age”, explains Ana Mª Cuervo, but, just as importantly, “we have shown that increase your activity it may be an effective strategy to slow down atherosclerosis and stop its progression.”
The study is the first to show that increasing chaperone-mediated autophagy could be an effective way to prevent atherosclerosis from worsening or progressing.
Cardiovascular disease (CVD) is the leading cause of death in the world, with more than 80% of those deaths due to heart attacks and strokes. In turn, it is often associated with atherosclerosis: the buildup of plaque (a sticky material consisting of fat, cholesterol, calcium, and other substances) within the walls of the arteries. accumulation of plate it hardens and narrows the arteries, preventing them from delivering oxygenated blood to the heart muscle (causing heart attacks), the brain (stroke), and the rest of the body.
In the study, the researchers up-regulated this process in mice fed a high-fat, proatherosclerotic diet and then compared them to control mice fed the same diet for 12 weeks.
They found that mice in which autophagy was genetically enhanced had greatly improved blood lipid profiles, with markedly lower cholesterol levels compared to control mice. Furthermore, the plaque lesions that formed in the genetically altered mice were significantly smaller and less severe compared to the plaques in the control mice.
Research has also found evidence that a weak autophagy it also correlates with atherosclerosis in people. Some stroke patients undergo a surgical procedure, known as a carotid endarterectomy, which removes plaque-affected segments of their carotid arteries to reduce the risk of a second stroke.
Dr. Cuervo’s team analyzed the activity of autophagy in segments of the carotid artery of 62 patients who had suffered a stroke who were followed up for three years after surgery and found that patients with “higher levels of autophagy after their first stroke never had a second stroke, whereas almost all patients with limited autophagy did experience a second stroke.
The Spanish researcher believes that, in principle, this strategy could become a way of preventing atherosclerosis, although she clarifies that “proposing it asthe preventive therapythat is, at the age of 50 you should take the pill that activates autophagy, it is not yet something that can be considered in clinical practice”, because, he points out, “preventive treatments require very long clinical trials”.
More feasible sees the fact that it is used “in people who have already had a heart attackbecause we have seen that these people who have low levels of autophagy are much more likely to have a second heart attack than those who have better autophagy activity.”
In fact, he anticipates that his team has developed pharmacological compounds which have shown promise in safely and effectively increasing autophagy activity in most mouse tissues and in human-derived cells.
These compounds, details ABC Health Dr. Cuervo decreases “a natural ‘brake’ that we all have on autophagy to keep it at levels that would be normal” and, “removing that natural ‘brake’ helps increase autophagy to levels similar to what a normal person would have.” healthy young person.
Although they are still in the preclinical phase, there is already a pharmaceutical company interested in taking them to clinical trials and the “idea is to start the first clinical trial in early 2023 to show that the compounds are safe.”
The researcher also warns that there are many types of autophagy and that in this case we are talking about the one mediated by chaperones because “it seems to us to be one of the safest”. Other forms of autophagy, she explains, “trap whatever they see into the cell.”
Chaperone-mediated autophagy also plays a role in neurodegenerative diseases, as reported last year by Dr. Cuervo’s team in «Cell» where it was shown that the progressive decrease that occurs with age in neurons contributes to the senile dementiabut that in the case of degenerative diseases such as Alzheimer’s, this reduction is even greater and using the “compounds that we have developed we could reduce memory loss and other symptoms in animal models of these diseases.”
In this sense, adds the researcher, there is now a lot of interest in what is called “geroterapeutics”, that is, “interventions that do not act on a specific disease, but what they do is prevent one or more of the changes that lead to aging and thereby prevent associated diseases, including metabolic disorders such as atherosclerosis. From this point of view, since the decrease in autophagy mediated by chaperones seems to occur with age in many organs, compounds that activate it could be good candidates as gerotherapy”.
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