Scientists have discovered that by accelerating a process that normally slows down as we age could actually be one way to protect people from one major cause of heart attacks and strokes.
Due to research done on mice, scientists have discovered that they can successfully minimize artery-narrowing plaque that causes adverse heart conditions. These findings have been published in the journal Proceedings of the National Academy of Sciences.
A research group at the Albert Einstein College of Medicine used a cellular process that was discovered back in 1993 but named in 2000, which is a process of boosting chaperone-mediated autophagy (CMA).
Professor of molecular biology and medicine, Dr. Ana Maria Cuervo, M.D. discovered the process, explaining, “We’ve shown in this research that we need CMA to protect against atherosclerosis, which becomes severe and progresses when CMA declines – something that also happens when people get older.”
She added, “But equally important, we’ve proven that increasing CMA activity can be an effective strategy for curbing atherosclerosis and halting its progression.”
What CMA does is ‘keeps cells functioning normally by selectively degrading the many proteins that cells contain.’ Dr. Cuervo has also decoded a number of the molecular players that are involved in CMA, showing that ‘through its timely degradation of key proteins, it regulates numerous intracellular processes – including glucose and lipid metabolism, circadian rhythms and DNA repair.’
Moreover, Dr. Cuervo also found that when CMA is disrupted, it also allows damaged proteins to accumulate to what are considered toxic levels, which contribute to aging. And when this toxic buildup happens in the nerve cells, it can contribute to other neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s disease.
How Researchers Are Finding Ways To Fight Against Plaque
The world’s leading cause of death is cardiovascular disease, which is normally linked to atherosclerosis. Atherosclerosis is a buildup of plaque with the walls of the arteries, made up of a sticky material that consists of cholesterol, calcium, fat, and other substances. When plaque accumulates and hardens, it narrows the arteries which prevents them from bringing necessary oxygenated blood to the heart muscle, which may led to heart attacks, or bringing blood to the brain, causing strokes, as well as to the rest of the body.
Dr. Cuervo is also the co-director of the Institute for Aging Research at Einstein, and she wanted to look into the role of CMA in atherosclerosis by studying it in mice, feeding them a typical fatty Western diet for 12 weeks and monitoring the CMA activity in their plaque-affected aortas. At first, their CMA activity increased as a result to the dietary challenge. But after 12 weeks, the plaque buildup was found to be substantial where basically no CMA activity could be detected in the two types of cells. These are the macrophages and the arterial smooth muscle cells which are known to malfunction during atherosclerosis, leading to the buildup of plaque within the arteries as a result.
Dr. Cuervo explained in a media release in Einstein, “CMA seemed to be very important in protecting macrophages and smooth muscle cells—helping them function normally despite the pro-atherosclerotic diet—at least for a while, until their CMA activity basically came to a halt.”
Dr. Cuervo and colleagues also noted that by feeding mice the high-fat diet that was completely lacking in CMA activity produced even more evidence of the importance of CMA, that ‘plaques nearly 40% larger than those in control animals that were also on the high-fat diet.’
Both In Mice and In Men
Meanwhile, the researchers also found evidence that weak CMA activity directly correlates with atherosclerosis in humans too. A number of patients that had strokes underwent surgical procedures called carotid endarterectomy. This procedure removes plaque-affected segments throughout their carotid arteries in order to lessen the risk of having another stroke. Dr. Cuervo and team also studied CMA activity in carotid artery segments from 62 first-stroke patients, following them for the next three years after their surgery.
“Those patients with higher levels of CMA following their first strokes never got a second one, while second strokes occurred in nearly all the patients with low CMA activity. This suggests that your CMA activity level post-endarterectomy could help in predicting your risk for a second stroke and in guiding treatment, especially for people with low CMA,” she said.
Published on PNAS, the study is the first to feature how turning up CMA could possibly be an effective way to lessen or prevent atherosclerosis from becoming severe or even progressing in the first place. The CMA-boosted mice showed substantially improved blood lipid profiles, as well as impressively reduced levels of cholesterol as compared with mice in the control group.
Moreover, the plaque lesions that formed in the genetically altered mice were also remarkably smaller and milder in severity when compared to the plaque in the control group mice. Thankfully, patients will not require genetic alternation in order to benefit from this particular finding.
Dr. Cuervo explained, “My colleagues and I have developed drug compounds that have shown promise for safely and effectively increasing CMA activity in most mouse tissues and in human-derived cells.”
After the findings of this study, the college has since filed for intellectual property on the technology.
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