Product Citations: 5

Inhibition of immunoglobulin E attenuates pulmonary hypertension.

In Nat Cardiovasc Res on 1 July 2022 by Shu, T., Liu, Y., et al.

Pulmonary hypertension (PH) is a severe cardiopulmonary disease characterized by pulmonary vascular remodeling. Immunoglobulin E (IgE) is known to participate in aortic vascular remodeling, but whether IgE mediates pulmonary vascular disease is unknown. In the present study, we found serum IgE elevation in pulmonary arterial hypertension (PAH) patients, hypoxia-induced PH mice and monocrotaline-induced PH rats. Neutralizing IgE with an anti-IgE antibody was effective in preventing PH development in mice and rat models. The IgE receptor FcεRIα was also upregulated in PH lung tissues and Fcer1a deficiency prevented the development of PH. Single-cell RNA-sequencing revealed that FcεRIα was mostly expressed in mast cells (MCs) and MC-specific Fcer1a knockout protected against PH in mice. IgE-activated MCs produced interleukin (IL)-6 and IL-13, which subsequently promoted vascular muscularization. Clinically approved IgE antibody omalizumab alleviated the progression of established PH in rats. Using genetic and pharmacological approaches, we have demonstrated that blocking IgE-FcεRIα signaling may hold potential for PAH treatment.
© 2022. The Author(s), under exclusive licence to Springer Nature Limited.

  • Cardiovascular biology

Inhibition of Immunoglobulin E Attenuates Pulmonary Hypertension

Preprint on Research Square on 4 November 2021 by Ting, S., Ying, L., et al.

Pulmonary hypertension (PH) is a severe cardiopulmonary disease characterized by pathological vascular remodeling in the lung. Immunoglobulin E (IgE) is known to participate in aortic vascular remodeling, but whether IgE mediates pulmonary vascular remodeling in PH is unknown. Here, we found serum IgE elevation in PAH patients, hypoxia-induced PH mice and monocrotaline (MCT)-induced PH rats. Combining animal model of PH with single-cell RNA sequencing, we found IgE production in the lung tissues of PH mice. Neutralizing IgE with an anti-IgE antibody was effective in preventing PH development in mice and rat models. The IgE receptor FcεRIα was also upregulated in PH lung tissues and Fcer1a deficiency prevented the development of PH in mice. Single-cell RNA-seq revealed that FcεRIα was mostly expressed in mast cells, and mast cell-specific Fcer1a knockout protected against PH in mice. Further mechanistic experiments revealed that IgE-activated mast cells produced interleukins IL6 and IL13, which subsequently promoted vascular muscularization. Clinically approved IgE antibody Omalizumab alleviated the progression of established PH in rats. Using genetic and pharmacological approaches, we have demonstrated that blocking IgE- FcεRIα signaling may hold potential for the treatment of PAH.

  • Mus musculus (House mouse)
  • Cardiovascular biology

Secondhand smoke exposure and endothelial stress in children and adolescents.

In Academic Pediatrics on 13 October 2014 by Groner, J. A., Huang, H., et al.

Links between secondhand smoke exposure and cardiovascular disease in adults are well established. Little is known about the impact of this exposure on cardiovascular status during childhood. The purpose of this study was to investigate relationships between secondhand smoke exposure in children and adolescents and cardiovascular disease risk--systemic inflammation, endothelial stress, and endothelial repair.
A total of 145 subjects, aged 9 to 18 years, were studied. Tobacco smoke exposure was determined by hair nicotine level. Cardiovascular risk was assessed by markers of systemic inflammation (C-reactive protein [CRP] and adiponectin); by soluble intercellular adhesion molecule 1 (s-ICAM1), which measures endothelial activation after surface vascular injury; and by endothelial repair. This was measured by prevalence of endothelial progenitor cells (EPCs), which are bone marrow-derived cells that home preferentially to sites of vascular damage.
Hair nicotine was directly correlated with s-ICAM1 (r = 0.4090, P < .0001) and negatively correlated with EPC prevalence (r = -0.2002, P = .0195). There was no relationship between hair nicotine and CRP, and a trend toward a weak relationship with adiponectin. Hair nicotine and body mass index were independent variables in a multivariate model predicting s-ICAM1; hair nicotine was the only significant variable in a model predicting EPC prevalence.
Secondhand smoke exposure during childhood and adolescence is detrimental to vascular health because s-ICAM1 is a marker for endothelial activation and stress after vascular surface injury, and EPCs contribute to vascular repair. The fact that body mass index is also a factor in the model predicting s-ICAM1 is concerning, in that 2 risk factors may both contribute to endothelial stress.
Copyright © 2015 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Flow cytometric measurement of SLAM-associated protein and X-linked inhibitor of apoptosis.

In Methods in Molecular Biology (Clifton, N.J.) on 12 February 2013 by Marsh, R. A., Bleesing, J. J., et al.

Flow cytometry is a valuable tool for the detection and characterization of proteins expressed by individual cells. Flow cytometry can be used to measure cell expression of 2 intracellular proteins that are involved in the regulation of immune homeostasis, SLAM-associated protein (SAP) and X-linked inhibitor of apoptosis (XIAP). These proteins are defective in patients with the immune deficiency X-linked lymphoproliferative disease (XLP), due to mutations in the SH2D1A and XIAP/BIRC4 genes, respectively (Coffey et al. Nat Genet 20:129-135 1998; Nichols et al. Proc Natl Acad Sci U S A 95:13765-13770, 1998; Sayos et al. Nature 395:462-469, 1998; Rigaud et al. Nature 444:110-114, 2006). This procedure describes a technique that can be efficiently used to detect SAP and XIAP by flow cytometry.

  • Biochemistry and Molecular biology

Flow-cytometric analysis of mouse platelet function.

In Methods in Molecular Biology (Clifton, N.J.) on 1 July 2004 by Nieswandt, B., Schulte, V., et al.

  • Biochemistry and Molecular biology
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