In Cardio Breakthrough, Researchers Prevent Clogged Arteries with Chaperone Mediated Autophagy

An article published in the Proceedings of the National Academy of Sciences (PNAS) highlights research conducted by Dr. Ana Maria Cuervo, M.D., Ph.D. to investigate the role chaperone-mediated autophagy (CMA) can play in preventing atherosclerosis, a type of thickening or hardening of the arteries caused by a buildup of plaque in the inner lining of an artery.

The published findings show that when protective CMA depletes as humans age, atherosclerosis is permitted to increase in severity. Unchecked development of atherosclerosis can go on to cause severe cardiovascular events, such as heart attacks and strokes.

Cardiovascular disease is the number one cause of death in the U.S., causing a death every 36 seconds according to statistics released by the U.S. Centers for Disease Control and Prevention (CDC). Annually, this places a $363 billion burden on the U.S. healthcare system. Many of the factors that contribute to cardiovascular issues are also related to age, such as inadequate physical activity and high blood cholesterol.  

Autophagy is the cellular process by which cells dispose of proteins and organelles, by using lysosomes. Acting as a natural form of immune defense, or innate immunity, CMA works as the taxi- or chaperone- to a lysosomal pathway. As malfunctioning proteins in a cell become too numerous, CMA will choose proteins that should be degraded to promote normal cell processes.

These chosen proteins are brought to lysosomes, which do their job to complete the degradation before recycling the residues leftover. Without a properly functioning CMA system, and therefore a functioning lysosomal process, the human body will accumulate damaged proteins. These damaged proteins can wreak havoc on the system and even lead to toxicity in nerve cells or neurodegeneration.  

This research was conducted at the Albert Einstein College of Medicine. In the article, titled "Protective role of chaperone-mediated autophagy against atherosclerosis" mice were fed a pro-atherosclerotic, high-fat diet for three months. Compared to control mice, CMA levels in blood lipid profiles were higher, with an added bonus of lower cholesterol. Plaque lesions, which build up and narrow arteries, had reduced in size and become milder. 

In summation, Cuervo found a link between CMA levels and atherosclerosis, on top of the link already known to neurodegenerative diseases, such as Alzheimer’s disease or Parkinson’s. Rather than having a patient undergo a carotid endarterectomy to remove the plaque that has built up in arteries, Cuervo intends to use her findings to find a way to prevent CMA levels from depleting as a person ages.  

Cuervo explained her summary of the published findings. "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… But equally important, we've proven that increasing CMA activity can be an effective strategy for curbing atherosclerosis and halting its progression," Cuervo said.

The article serves as Cuervo’s induction piece, as she was inducted into the National Academy of Sciences in 2019. The COVID-19 pandemic delated the publication of the article, but the findings are ground-breaking, nonetheless. Einstein intends to advance research further after obtaining intellectual property rights on this biotechnology.