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Published on: September 28, 2015
Allergic asthma aggravates angiotensin Ⅱ-induced cardiac remodeling in mice
Chi Geng1, Yufan Feng1, Yang Yang1
1Department of Pathophysiology, State Key Laboratory of Medical Molecular Biology Institute of Basic Medicine, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
Insights
Allergic asthma worsens heart failure and cardiac remodeling in mice. Blocking immunoglobulin E (IgE) signaling pathways improved heart function, suggesting anti-IgE therapy for heart conditions in asthma patients.
Area of Science:
- Cardiology
- Pulmonology
- Immunology
Background:
- Cardiovascular disease is a leading global cause of death, with heart failure (HF) as its advanced stage.
- Asthma, a common chronic respiratory condition, is linked to increased cardiovascular disease risk, but its specific impact on HF remains understudied.
- The mechanisms connecting asthma and HF are not well understood.
Purpose of the Study:
- To investigate the influence of asthma on heart failure (HF).
- To elucidate the underlying mechanisms by which asthma affects cardiac remodeling and function.
- To explore potential therapeutic targets for managing asthma-related cardiac complications.
Main Methods:
- Analysis of National Health and Nutrition Examination Survey data to assess the association between asthma and HF prevalence.
- Development of a mouse model combining ovalbumin (OVA)-induced allergic asthma and angiotensin II-induced cardiac remodeling.
- Evaluation of cardiac function, histological changes, immunoglobulin E (IgE) and FcεR1 expression, and downstream signaling in asthma models.
- Intervention using FcεR1-deficient mice and anti-IgE antibody to block IgE-FcεR1 signaling.
Main Results:
- A higher prevalence of HF was observed in individuals with asthma, indicating an independent association.
- OVA-induced asthma in mice led to impaired heart function and exacerbated cardiac remodeling.
- Asthma increased serum IgE levels and cardiac FcεR1 expression, activating downstream signaling pathways.
- Blocking IgE-FcεR1 signaling via genetic deficiency or antibody treatment ameliorated asthma-induced cardiac dysfunction and remodeling.
Conclusions:
- Allergic asthma adversely affects cardiac function and promotes cardiac remodeling.
- The IgE-FcεR1 pathway plays a critical role in mediating asthma's negative impact on the heart.
- Targeting the IgE-FcεR1 pathway, potentially with anti-IgE therapy, shows promise for treating heart conditions in asthma patients.
Abstract:
Cardiovascular disease remains the leading cause of death globally, and heart failure (HF) represents its terminal stage. Asthma, one of the most common chronic diseases, has been reported to be associated with an increased risk of cardiovascular disease. However, the link between asthma and HF has rarely been studied, and the possible mechanisms by which asthma affects HF are unclear. This study aimed to explore the influence of asthma on HF and the possible mechanisms. We analyzed data from the National Health and Nutrition Examination Survey and found a higher prevalence of HF among asthmatic individuals, and identified an independent association between HF and asthma. Subsequently, we produced mice with concurrent ovalbumin (OVA) sensitization-induced allergic asthma and angiotensin Ⅱ infusion-induced cardiac remodeling to explore the effect of asthma on cardiac remodeling in vivo. The results showed that OVA-induced asthma impaired heart function and aggravated cardiac remodeling in mice. We also found that OVA sensitization increased the expression levels of immunoglobulin E (IgE) in serum and IgE receptor (FcεR1) in the heart, and enhanced the activation of downstream signaling molecules of IgE-FcεR1 in the heart. Importantly, blockage of IgE-FcεR1 using FcεR1-deficient mice or an anti-IgE antibody prevented asthma-induced decline of cardiac function, and alleviated cardiac remodeling. These findings demonstrate the adverse effects of allergic asthma on the heart, and suggest the potential application of anti-IgE therapy in the treatment of asthma complicated with heart conditions.
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