New finding to prevent plaque buildup and heart attack/stroke

April 13, 2022
New finding to prevent plaque buildup and heart attack/stroke

The accumulation of damaged proteins contributes to ageing and disease – protecting against it requires boosting a cellular housekeeping process known as chaperone-mediated autophagy (CMA). CMA keeps cells functioning normally by selectively degrading the damaged proteins contained in cells.

The process was first discovered in 1993 by Dr. Ana Maria Cuervo, a Professor of Developmental and Molecular Biology and of Medicine, and Co-director of the Institute for Aging Research at Albert Einstein College of Medicine. Dr. Cuervo has shown that CMA regulates numerous intracellular processes including glucose and lipid metabolism, circadian rhythms, and DNA repair – an example of a faulty process is atherosclerosis, the buildup of plaque (a sticky substance consisting of fat, cholesterol, calcium, and others) within the walls of arteries.

In atherosclerosis, plaque deposits hardens and narrows arteries, impairing their key function of delivering oxygenated blood throughout the body. This can lead to events such as heart attacks and strokes, which are major factors of cardiovascular disease (CVD).

To investigate CMA’s role in atherosclerosis, Dr. Cuervo and colleagues promoted atherosclerosis in mice by feeding them a fat-heavy diet for 12 weeks and monitoring CMA activity in the animals’ aortas. CMA activity initially increased in response to the dietary challenge; but after 12 weeks, plaque buildup was significant, and virtually no CMA activity could be detected in either of two types of cells – macrophages and arterial smooth muscle cells.

“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,” said Dr. Cuervo.

CMA-boosted mice, however, had greatly improved blood lipid profiles, with markedly reduced levels of cholesterol than control mice. Conversely, plaques nearly 40% larger formed in mice totally lacking in CMA activity; they were also fed a high-fat diet.

There is evidence that weak CMA activity correlates with atherosclerosis in people too.

Dr. Cuervo and her colleagues noted CVD patients with higher levels of CMA after a carotid endarterectomy, a surgical procedure that removes plaque-affected segments of their carotid arteries, were spared a second stroke. “[…] 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,” Dr. Cuervo said.

Fortunately, people won’t need a genetic alteration to increase CMA activity as Dr. Cuervo and colleagues have developed drugs for this purpose.

Read: Heart attack predictions made by AI-powered tool

Category: Features, Top Story

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