New technology ‘sees’ how cholesterol causes heart attacks

The U.S. government’s top research agency has made an important discovery that could help create new drugs to lower “bad” cholesterol and hopefully prevent heart attacks and strokes.

But the interesting part of this story is not only the discovery itself, but also the technology responsible for it: a relatively new type of microscope that essentially froze LDL cholesterol molecules, allowing researchers to have the first time a detailed view of the structure of LDL cholesterol. LDL and finding new ways to approach stopping the buildup of LDL in the body.

technology, cryo-electron microscopyallowed scientists at the National Institutes of Health to see how LDL accumulates in the blood. The inventors of the microscope won the Nobel Prize in 2017 and this technology promises scientific advances of all kinds.

Research with the tool will 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, affects -C, accumulates in the body. , and causes heart attacks and strokes in people with genetically high LDL cholesterol levels.

This condition is known as familial hypercholesterolemia.

The genetic disease causes LDL (bad) cholesterol levels to increase and remain high. This disease appears at birth and can cause heart attacks at an early age, according to the U.S. National Institutes of Health.

Researchers hope the breakthrough will help scientists cure FH, which affects one in 250 Americans and increases the risk of dying from the disease. coronary artery disease at a younger age.

Currently, most people with FH treat it by taking statins or other medications. But until the NIH’s discovery in December, which allowed them to take a sort of frozen snapshot of the molecule, the actual way LDL accumulated in the body wasn’t completely understood.

The results provide new information that could one day lead to new types of drugs, said Dr. Alan Remaley, principal investigator of lipoprotein metabolism at the NIH. “Our results provide a potential new strategy to increase the ability of the LDL receptor to bind and clear LDL from the circulation,” Remaley explained.

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

The functioning of molecules is determined by their structures. “When we know their structures, we know how they work, how to repair them if they are faulty or how to stop them if they cause damage. Nature is the supreme molecular architect and we need techniques like cryogenics. -EM to see the details of what she’s building,” Finn explained.

Why LDL is bad

The breakthrough came when the NIH managed to preserve the structure of LDL, creating a kind of freeze frame that literally trapped the LDL in an ice form that allowed it to be seen under an electron microscope. The images were sent to a computer algorithm which then built a 3D model of the molecule.

Cryoelectronic machines cost between $2 million and $3 million per device and have become essential tools for modern biological and biological technologies. biomedical researchFinn said. Atlanta has two: 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 discovery, researchers couldn’t really observe the process.

LDL causes fatty deposits, called plaques, to build up in artery walls, which is a major cause of heart disease.

The purpose of LDL is not entirely harmful: its role 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 blood can get stuck in the arteries, triggering inflammation and narrowing 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). Eating too many foods high in saturated fat can increase LDL cholesterol.

Trans fats are found in margarine, shortening, baked goods and fried foods. They significantly raise LDL cholesterol 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 vegetable oils, said Dr. Danny J. Eapen, of the Cardiac Rehabilitation Center. from Emory St. Joseph Hospital and Emory University School of Medicine. Olive oil can also help reduce cholesterolespecially when replacing harmful fats such as butter and margarine, Eapen said.

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