Excess Cholesterol Provokes PERK Expression in Vascular Smooth Muscle Cells in Atherosclerosis
Atherosclerosis is a condition of localized excesses of cholesterol in blood vessel walls, leading to fatty plaques that narrow and weaken those vessels, ultimately leading to stroke or heart attack. A lot of attention is given to the way in which excess cholesterol induces dysfunction in the macrophage cells responsible for clearing that cholesterol from blood vessel walls, thereby creating a feedback loop in which atherosclerotic plaques grow. Researchers here instead look at the effects of excess cholesterol on smooth muscle cells, and how it draws them into making the problem worse.
"We are trying to identify new pathways that cause atherosclerotic plaque buildup, in particular pathways that involve a certain cell type, called smooth muscle cells. For many years, researchers have been focused on other cell types, like endothelial cells and macrophages, but more recent studies have highlighted a role of smooth muscle cells in plaque formation. We found that if we block a specific protein in smooth muscle cells, we can effectively block the majority of plaque formation from occurring in an animal model."
Using a knockout method, researchers fed genetically modified mice a high fat diet and caused the mice to have high cholesterol levels in their blood to drive atherosclerotic plaque formation. Blocking a specific protein called PERK in these mice resulted in an 80% decrease of atherosclerotic plaque buildup in male mice. "This tells us that blocking PERK in smooth muscle cells is important in plaque formation. Interestingly, this protein is activated in smooth muscle cells by too much cholesterol in the cells. There are a lot of drugs on the market that block the smooth muscle cell pathway. Now that we know this buildup can be blocked by targeting smooth muscle cells, we can use medication that is already available and target this pathway to help patients with atherosclerotic plaque buildup. This is just another way we can block or lower the plaque buildup, especially for those who are unable to prevent atherosclerosis with lifestyle modifications or statins."