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 now 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 FcεR1α 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 FcεR1 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.
- Jing Wang, Xiang Cheng, Mei-Xiang Xiang, Mervi Alanne-Kinnunen, Jian-An Wang, Han Chen, Aina He, Xinghui Sun, Yan Lin, Ting-Ting Tang, Xin Tu, Sara Sjφberg, Galina K. Sukhova, Yu-Hua Liao, Daniel H. Conrad, Lunyin Yu, Toshiaki Kawakami, Petri T. Kovanen, Peter Libby, Guo-Ping Shi. IgE stimulates human and mouse arterial cell apoptosis and cytokine expression and promotes atherogenesis in Apoe–/– mice. Journal of Clinical Investigation, 2011; DOI: 10.1172/JCI46028
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