Breakthrough technology sees how cholesterol causes heart attacks

Michael Scaturro, The Atlanta Journal-Constitution on Dec 27, 2024

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ATLANTA — The U.S. government’s premier research body has made an important discovery that could help create new drugs to lower “bad” cholesterol, and hopefully prevent heart attacks and stroke.

But the interesting part of that story isn’t just the discovery itself, but the technology responsible for it: a relatively new type of microscope that essentially froze LDL cholesterol molecules, allowing researchers for the first time to get a detailed view of the structure of LDL and find new ways to approach stopping LDL buildup into body.

The technology, cryo-electron microscopy, allowed National Institutes of Health scientists to view how LDL accumulates in the blood. The microscope’s inventors won the Nobel Prize in 2017, and the tech promises breakthroughs of all kinds in science.

Research with this tool is going to have serious health benefits, the NIH said, because it allowed them for the first time to see how “bad” cholesterol, known as low-density lipoprotein-cholesterol or LDL-C, builds up in the body, and causes heart attacks and strokes in people who have genetically high LDL cholesterol.

That condition is known as familial hypercholesterolemia.

The genetic disorder causes LDL (bad) cholesterol levels to spike and remain elevated. The condition begins at birth and can cause heart attacks at an early age, according to the U.S. National Institutes of Health.

The researchers hope the breakthrough will help scientists cure FH, which affects 1 in 250 Americans, and increases their likelihood of dying from coronary artery disease at a younger age.

Presently, most people who have FH treat it by taking statins or other drugs. But until the NIH discovery in December, which allowed them to take a sort of freeze-frame photo of the molecule, the actual way in which LDL accumulated in the body wasn’t completely understood. The findings provide new insights that one day can lead to new types of drugs, said Dr. Alan Remaley, senior investigator in lipoprotein metabolism at the NIH. “Our findings provide a potential new strategy for increasing the ability of the LDL receptor for binding and removing LDL from the circulation,” Remaley explained.

Dr. Aditi Das and Dr. MG Finn, both with Georgia Tech’s School of Chemistry and Biochemistry, explained in an email that the technology represents a revolution in biology and biochemistry because it allows scientists to determine the structures of biological molecules in great detail.

How molecules function is determined by their structures. “When we know their structures, we have a big clue as to how they work, how to fix them if they are defective, or how to stop them if they cause harm. Nature is the supreme molecular architect, and we need techniques like cryo-EM to see the details of what she builds,” Finn explained.

Why LDL is bad

The breakthrough came when the NIH was able to preserve the LDL’s structure, creating a sort of freeze-frame that literally trapped LDL in a form of ice that allowed it to be seen by an electron microscope. The images were sent to a computer algorithm that then built a 3D model of the molecule.

Cryo-electron machines cost between $2 million and $3 million per device, and have become essential tools for modern biological and biomedical research, Finn said. Atlanta has two of them: one at Georgia Tech, the other at Emory.

The fact that LDL cholesterol contributes to cardiovascular disease has been known for some time, but until the NIH finding, researchers couldn’t quite observe the process.

LDL causes fatty deposits, known as plaque, to build up in the walls of arteries, which is a major cause of heart disease.

LDL’s purpose isn’t entirely harmful: it’s job is to transport cholesterol to cells for energy, repair or hormone production.

But excess LDL is harmful, and the liver produces too much LDL when we eat unhealthy fats (like saturated and trans fats), which contributes to cardiovascular risk.

Excess LDL in the bloodstream can get stuck in the arteries, triggering inflammation and narrowing the blood vessels.

Over time, this plaque buildup can reduce blood flow or rupture, forming clots that block blood supply to the heart or brain, leading to heart attacks or strokes.

Saturated fats are found naturally in animal products (like butter, cheese, fatty meats) and some tropical oils (like coconut and palm oils). Overeating foods high in saturated fat can raise LDL cholesterol.

Trans fats are found in margarine, shortening, baked goods and fried foods. They raise LDL cholesterol significantly while lowering HDL (good) cholesterol, making them much more harmful, according to the American Heart Association.

For heart health, it’s best to replace these fats with unsaturated options like those found in fish, nuts, seeds, avocados and plant-based oils, said Dr. Danny J. Eapen, of the Cardiac Rehabilitation Center at Emory St. Joseph’s Hospital and Emory University School of Medicine. Olive oil can also help lower cholesterol, especially when it replaces harmful fats such as butter and margarine, Eapen said.

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