U.S. researchers found that immune cells cause cholesterol to be trapped in blood vessels, thus putting people with autoimmune diseases such as psoriasis, lupus and rheumatoid arthritis at high risk of developing cardiovascular disease.
Studying mice with a psoriasis-like condition, the researchers at Washington University School of Medicine in St. Louis found that the mice's blood vessels were stiff.
Cholesterol normally circulates freely between the blood and the tissues, but in these mice the inflexible vessel walls trapped cholesterol in their walls, promoting plaques that can cause heart attacks and strokes, according to the study published on Thursday in Cell Metabolism.
The researchers suspected that the walls of blood vessels also might be webbed with too much collagen. They created a light-sensitive form of high-density lipoprotein (HDL), the molecular carrying case for cholesterol, that fluoresces when hit with a laser beam, and inserted it into mice.
The researchers then induced a psoriasis-like disease in the mice by painting their ears with imiquimod, an inflammatory compound that activates the same kinds of immune cells that play a role in human psoriasis.
By following the fluorescent cholesterol carrier, the researchers could see that HDL cholesterol was delayed in getting out of the bloodstream in the mice that received the compound. This was true not only in the skin, but in internal arteries near the heart. In addition, the skin and blood vessels were more densely interlaced with collagen and more resistant to stretching.
When the researchers fed mice a high-cholesterol diet for three weeks while also painting their ears, the mice in the experimental psoriasis group developed significantly larger cholesterol deposits in their blood vessels.
"The skin-driven immune response can drive systemic changes," said senior author Gwendalyn Randolph, professor of immunology and a professor of medicine at the university. "Once immune cells are programmed by reactions to the inflamed skin, they move around the body to other skin sites and arteries to be ready for the next insult, enhancing the collagen density wherever they go."
An immune cell type called Th17 cells multiplies robustly in autoimmune diseases such as psoriasis, lupus and rheumatoid arthritis, releasing copious amounts of the immune molecule IL-17. When the researchers neutralized IL-17 in mice with psoriasis-like disease, using an antibody, collagen density went down and cholesterol deposits shrank.
People with psoriasis and lupus are two to eight times more likely to suffer a heart attack than people without these diseases. For young and middle-aged adults with rheumatoid arthritis, cardiovascular disease is the top cause of death.
