Allergic asthma aggravates angiotensin Ⅱ-induced cardiac remodeling in mice

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.

Keywords: AKT, protein kinase B; ANP, natriuretic peptide type A; Ang Ⅱ, angiotensin Ⅱ; BALF, bronchioalveolar lavage fluid; BMI, body mass index; BNP, natriuretic peptide type B; BW, body weight; CAD, coronary heart disease; COPD, chronic obstructive pulmonary disease; CVD, cardiovascular disease; EF, ejection fraction; FS, fraction shortening; HF, heart failure; HW, heart weight; IgE, immunoglobulin E; LVAW, left ventricular anterior wall; LVID, left ventricular internal dimension; LVPW, left ventricular posterior wall; NHANES, National Health and Nutrition Examination Survey; OVA, ovalbumin; TC, total cholesterol; TG, triglyceride; WGA, wheat germ agglutinin; WT, wild type; pSmad2/3, phosphorylated small mothers against decapentaplegic 2 and 3; α-SMA, α-smooth muscle actin; β-MHC, β-myosin heavy chain.