Understanding "Bad" Cholesterol: New Study Reveals Winning Strategy
A new study is offering a detailed glimpse into how "bad" cholesterol builds up in the body, paving the way for more personalized treatments for cardiovascular disease.
Scientists have long known that low-density lipoprotein-cholesterol, or LDL-C, plays a major role in heart disease, the world’s leading cause of death. Regularly cleaning LDL from the bloodstream is vital for good health. This vital clearance process hinges on a critical interaction between LDL and LDL receptors present on the surface of our cells.
A novel bit of good news: Scientists at the National Institutes of Health (NIH) have deciphered the structure of this exact connection. This groundbreaking work, published in Nature, reveals how LDL-C interacts with its receptor, paving the way for even more targeted therapies for high cholesterol.
"LDL is one of the main drivers of heart disease which kills one person every 33 seconds, so if you want to understand your enemy, you want to know what it looks like,” said Dr. Alan Remaley, M.D., Ph.D., co-senior author on the study.
When LDL binds to its receptor, the process of clearing LDL from the blood usually begins. But things can go awry when genetic mutations interfere with this process, causing LDL to build up, ultimately leading to blockages in the arteries (atherosclerosis).
Utilizing a powerful imaging technique known as cryo-electron microscopy, researchers were able to visualize the entire LDL structure, specifically focusing on its interaction with the LDL receptor.
"LDL is enormous and varies in size, making it very complex," explained Dr. Joseph Marcotrigiano, Ph.D., co-senior author on the study.
"No one’s ever gotten to the resolution we have. We could see so much detail and start to tease apart how it works in the body."
Using these detailed structural images in conjunction with advanced AI-powered prediction software, the researchers were able to pinpoint specific areas where LDL binds to the receptor.
This serves as groundbreaking insight into why some individuals inherit a condition called familial hypercholesterolemia (FH). Individuals with FH often experience extremely high levels of LDL at a young age. "We found that FH-associated variants tended to cluster in particular regions on LDL."
The study findings open up several exciting avenues. First, they could lead to improved diagnostic and treatment strategies specifically targeting areas where mutations disrupt the LDL-receptor connection.
Second, this discovery offers a clearer understanding of the mechanism of statins, a common heart disease medication that helps lower LDL. By knowing precisely where and how LDL binds to its receptor, researchers may now be able to refine statin treatments, making them even more effective.
Because this research sheds light on the precise interaction between these two entities – LDL and its receptor – this discovery may also open doors to design novel drugs that specifically target this interaction, offering a new class of therapies for high cholesterol and heart disease.
