Researchers prove direct link between immunoglobulin E and atherogenesis

August 9, 2011

There is an observed correlation between Immunoglobulin E (IgE) levels atherosclerosis, with twice amount of IgE present in patients with acute myocardial infarction as in patients with stable angina or without coronary heart disease (CHD). Guo-Ping Shi, DSc, Jing Wang, MD, PhD, and colleagues in the Department of Medicine at Brigham and Women's Hospital (BWH), have demonstrated the direct participation of IgE in atherogenesis in a mouse model. These findings appear in the August 8, 2011 issue of Journal of Clinical Investigation.

Mechanistic studies demonstrated that IgE contributes to atherogenesis by stimulating macrophage and cell and endothelial cell apoptosis and inflammatory molecule expression. Using IgE receptor FcR1alpha KO mice, the researchers demonstrated that inactivation of IgE activity reduced atherosclerotic lesions by 50% in aortic arches and >70% in thoracic-abdominal aortas.

The researchers first discovered that IgE activities require a complex formation between IgE receptor FcR1 and TLR4. Lack of any one of these receptors abolished completely IgE activities. These novel discoveries are important in any IgE-associated human disease study.

They also found that IgE induces macrophage apoptosis by activating a proton pump molecule NHE-1 (Na-H+ exchanger-1), thereby reducing extracellular pH. Both human and mouse macrophages undergo apoptosis in acidic pH. Absence or pharmacological inactivation of

NHE-1 abolished IgE-induced macrophage apoptosis and inflammatory molecule expression. Indeed, in human atherosclerotic lesions, areas rich in IgE and macrophages are acidic and filled with apoptotic cells.

Further studies may investigate how Anti-IgE monoclonal antibodies may become a novel therapy for atherosclerosis.

Related Stories

Recommended for you

New 'Tissue Velcro' could help repair damaged hearts

August 28, 2015

Engineers at the University of Toronto just made assembling functional heart tissue as easy as fastening your shoes. The team has created a biocompatible scaffold that allows sheets of beating heart cells to snap together ...

Fertilization discovery: Do sperm wield tiny harpoons?

August 26, 2015

Could the sperm harpoon the egg to facilitate fertilization? That's the intriguing possibility raised by the University of Virginia School of Medicine's discovery that a protein within the head of the sperm forms spiky filaments, ...

Research identifies protein that regulates body clock

August 26, 2015

New research into circadian rhythms by researchers at the University of Toronto Mississauga shows that the GRK2 protein plays a major role in regulating the body's internal clock and points the way to remedies for jet lag ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.