Researchers have found a new strategy to prevent arterial blockage

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By improving the process that slows down with age, you can prevent atherosclerosis, the main cause of heart attacks and strokes.According to the survey results published online today Minutes of the National Academy of Sciences ((((PNAS), Scientists at Albert Einstein Medical College, led by Dr. Ana Maria Cuervo, have succeeded in minimizing arterial stenotic plaques in mice that would otherwise develop these lesions. Researchers have achieved this by enhancing autophagy (CMA) via chaperones. This is a cell housekeeping process discovered by Dr. Quervo in 1993 and named in 2000.

“This study showed that CMA is needed to protect against atherosclerosis. Atherosclerosis becomes severe and progresses as CMA decreases. This is what people do. It also happens when we get older. ” Molecular biology In the field of medicine, he is the chair of Robert and Rene Belfer for the study of neurodegenerative diseases and co-director of the Einstein Institute for Aging. “But equally important is the increase in CMA activity. Effective strategy To control atherosclerosis and stop its progression. “

Impressive CMACV

CMA keeps cells functioning normally by selectively degrading many proteins contained in them. In CMA, special “chaperone” proteins bind to proteins in the cytoplasm, leading them to an enzyme-filled cell structure called lysosomes, which are digested and recycled. Dr. Quervo deciphers many of the molecular players involved in CMA, where CMA regulates numerous intracellular processes such as glucose and lipid metabolism, circadian rhythms, and DNA repair through timely degradation of key proteins. I showed that.She also discovered that destroyed CMA allows the accumulation of damaged proteins. Toxicity levelWhen it contributes to aging and accumulates toxicity in nerve cells, it contributes to neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease.

Dr. Quervo’s achievements were recognized in 2019 when she was elected to the National Academy of Sciences (NAS). In 1996, NAS began calling on newly elected members to submit special inaugural articles. PNAS It will emphasize the scientific contributions of the members. Today’s treatise on the protective role of CMA against atherosclerosis due to the pandemic-related delay of COVID-19 is Dr. Quervo’s inauguration. PNAS Add to the body of her work on the importance of paper and CMA.

Fight against plaque

Cardiovascular disease (CVD) is the leading cause of death worldwide and accounts for more than 80% of these CVD deaths from heart attacks and strokes. Second, CVD is usually associated with atherosclerosis. Accumulation of plaque (a sticky substance consisting of fat, cholesterol, calcium, and other substances) in the arterial wall. When plaque builds up, the arteries harden and narrow, preventing oxygenated blood from being pumped into the arteries. Myocardium To the brain (which leads to a heart attack), the brain (stroke), and the rest of the body.

To investigate the role of CMA in atherosclerosis, Dr. Quervo and colleagues fed a fatty Western diet for 12 weeks and monitored the CMA activity of the aorta of plaque-affected animals in mice. Promoted atherosclerosis. CMA activity initially increased in response to dietary challenges. However, after 12 weeks, plaque accumulation is prominent, dysfunctional due to atherosclerosis, and two types of cells known to accumulate plaque in the arteries (macrophages and arterial smooth muscle cells). So, CMA activity was virtually undetectable.

“CMA appears to be very important in protecting macrophages and smooth muscle cells, and despite a diet of atherosclerosis, CMA activity basically ceases for at least some time. Until then, it helps them function properly, “said Dr. Quervo. She said feeding mice that were completely deficient in CMA activity a high-fat diet provided stronger evidence of the importance of CMA. High-fat diet..

Mouse and male

Researchers have found evidence that weak CMA activity also correlates with atherosclerosis in people. Some patients who have had a stroke Carotid endarterectomyRemoves the affected area of ​​the carotid plaque and reduces the risk of a second stroke. Dr. Quervo and her colleagues analyzed CMA activity in the carotid segment from the first 62-Stroke patient He was followed up for 3 years after surgery.

“Patients with high levels of CMA after the first stroke did not develop a second stroke, but a second stroke occurred in almost all patients with low CMA activity,” said Dr. Cuervo. I have. “This suggests that CMA activity levels after intimal resection may help predict the risk of a second stroke and guide treatment, especially for people with low CMA.”

Raise CMA and regulate atherosclerosis

This study is the first to show that raising CMA may be an effective way to prevent atherosclerosis from becoming more severe or progressing. Researchers genetically “upregulated” CMA in mice fed a high-fat western diet with atherosclerosis and then compared the same diet to control mice fed for 12 weeks. .. CMA-boosted mice had significantly improved blood lipid profiles and significantly lower cholesterol levels compared to control mice. Plaque lesions formed in genetically modified mice were significantly less severe and milder than those in control mice. Fortunately, people do not need genetic modification to benefit from this discovery.

“My colleagues and I have developed a drug compound that has been shown to have the potential to safely and effectively increase CMA activity in most mouse tissues and human-derived cells,” said Dr. Cuervo.Einstein submitted intellectual property About this underlying technology.

The title of the PNAS treatise is “The Protective Role of Chaperone-mediated Autophagy Against Atherosclerosis”.

Removing protein may reduce cardiovascular disease

For more information:
Protective role of chaperone-mediated autophagy against atherosclerosis, Minutes of the National Academy of Sciences (2022). DOI: 10.1073 / pnas.2121133119..

Quote: Researchers have obtained a new strategy to prevent arterial blockages obtained from on March 28, 2022 (3 2022). 28th of March) was found

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Researchers have found a new strategy to prevent arterial blockage

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