Boston, MA - 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 vascular smooth muscle cell and endothelial cell apoptosis and inflammatory molecule expression. Using IgE receptor FcR1alpha 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 FcR1 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.
The National Heart, Lung, and Blood Institute, National Institutes of Health, USA, and National Natural Science Foundation of China funded this research.
Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare, an integrated health care delivery network. BWH is the home of the Carl J. and Ruth Shapiro Cardiovascular Center, the most advanced center of its kind. BWH is committed to excellence in patient care with expertise in virtually every specialty of medicine and surgery. The BWH medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in quality improvement and patient safety initiatives and its dedication to educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), www.brighamandwomens.org/research , BWH is an international leader in basic, clinical and translational research on human diseases, involving more than 900 physician-investigators and renowned biomedical scientists and faculty supported by more than $537 M in funding. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative. For more information about BWH, please visit www.brighamandwomens.org