Heart HealthScientists Uncover Hidden Pathway That Drives Cholesterol Buildup in the Liver
Researchers at UC San Diego have identified a previously unknown molecular pathway that explains why eating high-cholesterol foods raises LDL levels in the blood. When you consume excess dietary cholesterol, a set of proteins called Ral GTPases become activated in liver cells. This triggers a chain reaction that shuttles LDL receptors — the proteins responsible for clearing cholesterol from the blood — to cellular waste compartments called lysosomes, where an enzyme called cathepsin A destroys them. With fewer LDL receptors available, cholesterol accumulates in the bloodstream. Crucially, this process operates independently of PCSK9, the target of currently approved cholesterol-lowering drugs. Blocking cathepsin A pharmacologically restored LDL receptor levels and improved cholesterol clearance in experimental models, pointing toward an entirely new drug target for cardiovascular disease.
