Even when mice have too much PCSK9 and high cholesterol, if they have less of the CAP1 protein, their artery plaques don’t get as bad — proving CAP1 is needed for PCSK9 to cause inflammation.

PCSK9, a protein in the blood, sticks to another protein called CAP1 on immune cells, which turns on a chain reaction that makes the cells more inflamed and sticky, even if cholesterol levels are normal — this can worsen artery plaque.

PCSK9 doesn’t just cause inflammation — it also tricks immune cells into making more PCSK9, creating a cycle that keeps the inflammation going in artery plaques.

People with heart disease have higher levels of PCSK9 in their blood, and that’s linked to higher activity of inflammation proteins in their immune cells — even when their cholesterol is low from taking statins.

PCSK9 doesn't just raise bad cholesterol — it also directly worsens artery disease by making immune and blood vessel cells absorb more damaged fats, reducing their ability to clean out cholesterol, and increasing inflammation in the arteries.

A new drug called CAP1-hFc that blocks PCSK9 from sticking to CAP1 works better at reducing inflammation in immune cells than current PCSK9 drugs like evolocumab, which only lower cholesterol.