LDL-binding protein a target for new cholesterol-reducing therapies

Blood
A newly found protein that transports LDL into cells could point to new anticholesterol treatments.

Researchers led by Yale University have singled out a protein that is responsible for transporting LDL cholesterol into cells. This target could lead to new treatments for LDL buildup, which can cause atherosclerosis and heart disease.

Cholesterol and fats accumulate in arteries when they bind to lipoproteins in the body. And while scientists have long believed that the LDL receptor protein is responsible for the transport of LDL from the blood into cells, they've never been able to explain why people who do not have the receptor can still have high levels of LDL. To find an answer, the Yale-led team examined more than 18,000 genes from the inner lining of human blood vessels, according to a statement.

Their study, published in Nature Communications, found that a protein, ALK1, binds directly to LDL cholesterol and enables it to enter cells. This previously unknown pathway also promotes the transport of LDL from the blood into tissue, according to the statement.

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“The discovery of ALK1 as an LDL-binding protein implies that it might initiate the early phases of atherosclerosis,” said William Sessa, a professor of pharmacology and cardiology at Yale and a senior author of the paper. The “LDL-ALK1 pathway” could serve as a target for small molecules or antibodies, he said. Such treatments could be used in combination with current therapies to ward off or delay arterial buildup and heart disease.

There are a number of treatments for heart disease, including beta blockers to reduce blood pressure and angioplasty or stenting procedures to unblock arteries and keep them open. But the most common way to fight atherosclerosis before it occurs is to use lipid-lowering statins to keep LDL levels down.

Other research has found that the small molecule SRT1720, which targets the sirtuin 1 protein, extended the average life span of mice, while reducing body fat percentage and lowering LDL cholesterol levels. And a Queen Mary University-led team identified the enzyme ADAMTS7 as a key driver in the buildup of cells in blood vessels that leads to coronary artery disease.

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