Heart HealthHidden Ral-CTSA pathway lets dietary cholesterol erode liver LDL receptors, and blocking it lowers LDL
High cholesterol is a major driver of heart disease, the world's leading cause of death. Researchers at UC San Diego School of Medicine have uncovered a hidden pathway explaining why eating a lot of cholesterol weakens the liver's ability to clear LDL, the so-called bad cholesterol. In mice and human cells, dietary cholesterol activated a protein called Ral. Ral set off a chain of events involving an enzyme called cathepsin A (CTSA), which led to the loss of LDL receptors, the docking stations on liver cells that pull LDL from the blood. When the team blocked CTSA with a small-molecule inhibitor, LDL receptors became more stable and circulating LDL fell sharply in mice. The experimental drug has already passed an early human safety trial, which could speed development. The work, published in Nature, is preclinical, so it is not yet a treatment people can use, but it points to a new route beyond statins and PCSK9 inhibitors.
