The role of immunoglobulin E and mast cells in hypertension

Hypertension is the major cause of cardiovascular diseases and global mortality. Immunoglobulin E (IgE), which plays crucial roles in allergic diseases, has been implicated in the pathogenesis of vascular and cardiac remodeling via its receptor (FcεR1). In this study, we aimed to reveal the role of IgE and FcεR1 in hypertension.Herein, we reported that IgE levels were significantly increased in hypertensive patients as well as in hypertensive mice induced by angiotensin II (Ang II). Ang II-induced vascular remodeling and hypertension were significantly alleviated in FcεR1 genetic knockout mice or in mice treated with anti-IgE monoclonal antibody. Similarly, treatment with omalizumab (a clinical IgE antagonist) also markedly inhibited Ang II-induced hypertension. Furthermore, the cellular contribution of IgE-FcεR1 in hypertension was evaluated in mice with FcεR1 conditional knockout in mast cell (MC), smooth muscle cell (SMC), or endothelial cell (EC). Our data revealed that IgE-mediated hypertension is largely dependent on FcεR1 in MCs but not SMCs and ECs. Finally, RNA-seq and signaling pathway analyses of mouse bone marrow-derived mast cells (BMMCs) suggested that interleukin 6 (IL-6) is one of critical mediators in IgE-mediated hypertension. IL-6 derived from IgE-stimulated MCs promoted reactive oxygen species (ROS) production and decreased the levels of phosphorylated endothelial nitric oxide synthase (p-eNOS) in ECs, leading to endothelial dysfunction.Our findings reveal that IgE contributes to the pathogenesis of hypertension, at least partially through activating the IgE-FcεR1 signaling in MCs. Thus, IgE may represent a new therapeutic target for IgE-mediated hypertension.We defined a correlationship between high serum IgE levels and hypertension in humans and mice. We demonstrated that IgE played a critical role in mediating Ang II-induced hypertension dependent on its receptor FcεR1 in mast cells; Anti-IgE antibodies, including the clinical drug omalizumab, suppress Ang II-induced pathological vascular remodeling and hypertension. These findings suggest that IgE-FcεR1 represents novel molecular targets for hypertension, especially for the hypertensive patients with high serum levels of IgE or with history of allergic diseases.