Scientists could be one step closer to a solution to atherosclerosis by preventing the buildup of plaques that clog the arteries and lead to strokes and heart attacks.
What is atherosclerosis?
Atherosclerosis is the accumulation of cholesterol-containing plaques in the walls of arteries; this causes them to narrow, leading to reduced blood flow, higher blood pressure, and an increased risk of a heart attack or stroke. Atherosclerosis is the number one cause of death globally, and, by far, the highest risk factor for this disease is aging, although there are lifestyle factors, such as poor diet, smoking, obesity, and being sedentary.
Drugs such as statins attempt to manage the symptoms but are not truly effective in combating this disease, as they do not address the underlying cause: the formation of the sticky plaques that clog the arteries. Scientists such as Dr. Aubrey de Grey from the SENS Research Foundation have long been advocating for therapies that remove or prevent the formation of plaques altogether, as this would address the problem directly.
One step closer to a solution
In the journal Circulation, researchers at the La Jolla Institute for Allergy and Immunology have published a new study that supports the possibility that there are ways to prevent the formation of plaques in the first place . The team has reported the successful vaccination of atherosclerotic model mice by using a small piece of protein cut from “bad cholesterol”, which facilitates the formation of plaques.
The vaccine was shown to reduce plaque in the mice, and the team also identified the T cells most likely responsible for positive outcomes in human blood samples as part of the same study. The researchers suggest that this technique could form the basis of a vaccine for people.
The vaccine works by boosting the activity and numbers of a type of T cell responsible for reducing inflammation, which leads to a reduction of plaque formation. We have talked about therapies that modulate the immune system and change the ratio of immune cells multiple times, and it is looking like an increasingly promising avenue of research.
“Bad cholesterol” is an amalgam of cholesterol, which is a lipid, and its carrier, low-density lipoprotein (LDL). In order to create the vaccine, the team engineered a peptide that represents a short section of LDL.
The team mounted this peptide on a scaffold called a tetramer and exposed it to immune cells to see which ones became activated in its presence. They tested human blood from two groups of women, one with plaques and one without, to see which immune cells responded to the presence of the peptide.
They observed that a type of regulatory T cell (Tregs) was activated in both groups, although the numbers of Tregs was much lower in subjects with plaques than subjects without, as were the presence of other types of T cells. This suggests that the function of Tregs is somehow hampered by the inflammation that atherosclerosis causes.
The next generation of vaccines that offer greater utility
As well as having the potential to address atherosclerosis, this research spotlights the utility of next-generation vaccines. The immunogenic component of traditional vaccines is a cocktail of molecules harvested from dead or weakened pathogens, but this approach does not work against non-infectious diseases like cancer and atherosclerosis; these next-generation vaccines are much more specific, as they can regulate the immune response using just a single peptide. This means vaccines that target non-infectious diseases are now possible, and, as they are highly targeted, they should have fewer unwanted side effects.
The results presented in this paper show that an effective vaccine against atherosclerosis is now potentially possible. However, the researchers do caution that there is more research to be done before this vaccine can be translated to human use.
While statins simply try to treat the symptoms, a therapy that prevents the buildup of plaques in the first place would be a very welcome step in the battle against age-related diseases and the suffering they bring. If the therapy can be translated to people, it would make strokes and heart attacks practically a thing of the past, and that day cannot come soon enough.
 Kimura, T., Kobiyama, K., Winkels, H., Tse, K., Miller, J., Vassallo, M., … & Jenkins, M. K. (2018). Regulatory CD4+ T Cells Recognize MHC-II-Restricted Peptide Epitopes of Apolipoprotein B. Circulation, CIRCULATIONAHA-117.