Drugs that reduce cholesterol, like statins, can treat existing heart disease, but what if there was way to prevent heart disease from happening in the first place? This is the idea behind a new anti-atherosclerosis vaccine developed by scientists from the La Jolla Institute for Allergy and Immunology.
Atherosclerosis is a disease characterized by plaque buildup in the arteries. Plaques can be made up of all kinds of substances, including cholesterol, cellular waste products, calcium, and fibrin. As plaque collects on vessel walls, arteries grow thicker, narrowing the space for blood, carrying oxygen and nutrients, to flow through to reach tissues all over the body. Because of this, atherosclerosis can be a precursor to all sorts of heart disease: coronary heart disease, angina, carotid artery disease, peripheral artery disease, and chronic kidney disease.
Being able to prevent plaque buildup would be a game-changer in the world of heart health, because many people affected by atherosclerosis are unaware of their condition.
"Men in their 50's with apparently normal cholesterol may be at risk," explained senior author Klaus Ley, MD. "Only [after a heart attack would] their [doctors] realize they had atherosclerotic disease."
Vaccination is a viable solution to preventing this scenario. Researchers tested this possibility first in atherosclerotic mice. They vaccinated the mice with a piece of LDL (“bad”) cholesterol and saw that it successfully reduced plaque levels. To do so they extracted a piece of the core LDL protein.
Using that same approach, researchers tested the ability of the protein to attract immune cells in human blood samples. The samples were taken from women with and without plaque accumulation in the carotid arteries. From this experiment, researchers found a specific type of T cells responsible for the positive outcomes observed in the experiment with mice.
"We knew atherosclerosis had an inflammatory component but until recently didn't have a way to counteract that," Ley explained. "We now find that our vaccination actually decreases plaque burden by expanding a class of protective T cells that curb inflammation."
These protective T cells are CD4+ regulatory T cells (Tregs). Compared to blood samples from women without plaques, there were significantly less Tregs in the samples from atherosclerotic women. Instead of Tregs, researchers identified different types of T cells that were not as common in samples without plaque formation. Researchers are theorizing that during the development of heart disease, T cells experience a molecular change that prevents them from targeting atherosclerotic plaques.
"Once we can manipulate the immune response with a single peptide or epitope, we will be able to create more highly targeted vaccines with fewer non-specific responses,” Ley explained.
The potential vaccine would likely be given in addition to statin drugs. The next step? Develop an effective human vaccine.
The present study was published in the journal Circulation.
Sources: La Jolla Institute for Allergy and Immunology, American Heart Association
