A natural antibody prevents atherosclerosis in mice
Phospholipids, which are a class of lipids, are the primary building blocks of cellular membranes and membranes surrounding organelles. They possess multiple functions, such as forming permeability barrier, providing a surface for catalytic reactions, and participating in signal transduction.
Because of their chemical properties, phospholipids are highly prone to modification by reactive oxygen species. Phospholipids tend to undergo lipid peroxidation to form Oxidized phospholipids (OxPL), which can induce cytotoxicity and apoptosis and is known to have a key role in inflammation. Accumulating evidence indicates that OxPL is involved in the pathogenesis of atherosclerosis, a chronic inflammatory disease of arteries.
In atherosclerosis, plaque builds up in the arteries, resulting in narrowing and hardening of the arteries, which restricts blood flow. At its early stages, atherosclerosis usually doesn't cause any signs and symptoms. But when the arteries are severely damaged, it can cause a medical emergency, such as a heart attack, or a stroke. So, it's very important to avoid the development of atherosclerosis, and for people who already have atherosclerosis, interventions to prevent the condition from getting worse are in need.
Scientific research has suggested that OxPLs affect the function of all vascular wall cells, are able to stimulate an inflammatory response, and play a key role in all stages of atherosclerosis. A better understanding of OxPLs may inform novel strategies to deal with atherosclerosis.
Researchers from the University of California (UC) in the US has been studying OxPLs for a while. In previous work, the team demonstrated that E06, a natural IgM antibody to OxPLs, can inhibit the proinflammatory properties of OxPL.
In the latest study, UC researchers teamed up with those from La Jolla Institute for Allergy and Immunology, UT Southwestern Medical Center in the USA, the University of Eastern Finland in Finland, Medical University of Vienna, Center for Molecular Medicine of the Austrian Academy of Sciences in Austria, and Taipei Medical University in Taiwan, to further investigated the role of OxPL in vivo in plaque formation.
They generated transgenic mice that expressed part of the E06 antibody. They observed that E06 antibody fragment was produced in the animals' body and was released into the blood to suppress OxPL-induced inflammatory signaling. When fed a high-cholesterol diet that increases the risk of atherosclerosis, mice expressing the E06 fragment were much less likely to develop atherosclerosis, than mice that did not express it. In addition, mice expressing the E06 fragment lived much longer.
These results, collectively, indicate that the E06 antibody and other therapies that inactivate OxPL represent a potential strategy to inhibit atherosclerosis development.
OxPL are widely formed in inflammatory tissues. The new study proves the pro-inflammatory and pro-atherogenic of OxPL. The negative effects of OxPL can be prevented by E06 antibody.
According to senior author of the study, Dr. Joseph Witztum from UC, whose research is mainly focused on how oxidation of lipoproteins causes atherosclerosis, their study would have applications in the management of diseases like atherosclerosis, aortic stenosis, and hepatic steatosis.
The study, titled "Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice," can be read in the journal Nature.