373. They also trigger the expression of an innate immune receptor that makes the arteries more fat friendly.
Recent data suggest that the immune receptor in question, Toll-like receptor (TLR) 2, which recognizes bacterial lipids, might also enhance atherosclerosis—a disease that can lead to restricted blood flow due to the accumulation of fat in blood vessels. Mice that are plaque prone because they cannot properly dispose of fat stay plaque free if TLR2 is knocked out. Its loss from immune cells alone, however, does not protect these mice, suggesting that TLR2 on a nonimmune cell favors plaque growth.
Mullick et al. now find that TLR2 is expressed on the endothelial cells that line the curves of blood vessels. These cells are plaque prone by nature; the uneven blood flow here stimulates them to express more adhesion molecules and chemokines. They thus attract both circulating fat and macrophages that eat the fat and then harden into plaques. A high-fat diet thus increases plaque formation in part by giving macrophages more to chew on.
A high-fat diet also increased endothelial TLR2 levels in the atherosclerosis-prone mice, the authors found. Components of dietary fat may bind to TLR2 and thereby increase expression of the receptor on endothelial cells. These mice accumulated larger fat deposits and more macrophages in vessel curves than did their TLR2-deficient counterparts. The team has yet to determine how TLR2 expands plaques. Perhaps, like uneven blood flow, it increases endothelial cell adhesion molecule or chemokine levels.