Interleukin-18 Expression Increases in the Aorta and Plasma of Patients with Acute Aortic Dissection

Haiying Hu,Wenjing Liu,Liying Han,Chao Chang,Huanli Hu,Guangtai Zhang,Liping Duan,Jixiang Liu,Shuanli Xin,Xiufeng Zhao,Xinshun Huang

doi:10.1155/2019/8691294

Abstract

Background Interleukin- (IL-) 18 is a proinflammatory cytokine related to cardiovascular diseases, including hypertension and atherosclerosis. This study is aimed at determining whether IL-18 is related to aortic dissection (AD) and identifying the underlying mechanisms. Methods IL-18 expression in human aorta samples from AD (n = 8) and non-AD (NAD, n = 7) patients was measured. In addition, the IL-18, IL-6, interferon- (IFN-) γ, and IL-18-binding protein (IL-18BP) concentrations in plasma samples collected from the NAD and AD patients were detected. The effects of IL-18 on macrophage differentiation and smooth muscle cell (SMC) apoptosis were investigated in vitro. Results IL-18 expression was significantly increased in the aorta samples from the AD patients compared with those from the NAD patients, especially in the torn section. Aortic IL-18 was mainly derived from macrophages and also partly derived from CD4+ T lymphocytes and vascular SMCs. Plasma IL-18, IFN-γ, and IL-6 levels were significantly higher in the AD group than in the NAD group, and the IL-18 levels were positively correlated with the IFN-γ and IL-6 levels. In addition, plasma IL-18BP and free IL-18 levels were also elevated in the AD group. Linear regression analysis showed that the IL-18 level was independently associated with the presence of AD. In addition, anti-mouse IL-18-neutralizing monoclonal antibodies (anti-IL-18 nAb) inhibited angiotensin II-induced M1 macrophage differentiation and SMC apoptosis in vitro. Conclusion IL-18 may participate in AD by regulating macrophage differentiation and macrophage-induced SMC apoptosis.

Highlights

Given its features of acute onset, rapid development, and high morbidity and mortality, acute aortic dissection (AD) is a severe cardiovascular disease
There were no significant differences in age, gender, uncontrolled blood pressure (HBP), smoking, the fasting glucose (Glu) level, systolic blood pressure (SBP), diastolic blood pressure (DBP), the total cholesterol (TC) level, the total triglyceride (TG) level, the high-density lipoprotein cholesterol (HDL-C) level, the low-density lipoprotein cholesterol (LDL-C) level, the creatinine (CREA) level, or heart rate (HR) between the thoracic aortic dissection (TAD) group and the control group
The results showed that IL-18 was mainly expressed in macrophages, small amounts were expressed in T lymphocytes and vascular smooth muscle cells (SMCs) in human thoracic aortic tissue (Figure 1(d))

Summary

Introduction

Given its features of acute onset, rapid development, and high morbidity and mortality, acute aortic dissection (AD) is a severe cardiovascular disease. IL-18 has been reported to be involved in many inflammatory and immune diseases by promoting the expression of other proinflammatory cytokines. IL-18 expression in human aorta samples from AD (n = 8) and non-AD (NAD, n = 7) patients was measured. The IL-18, IL-6, interferon- (IFN-) γ, and IL-18-binding protein (IL-18BP) concentrations in plasma samples collected from the NAD and AD patients were detected. Aortic IL-18 was mainly derived from macrophages and partly derived from CD4+ T lymphocytes and vascular SMCs. Plasma IL-18, IFN-γ, and IL-6 levels were significantly higher in the AD group than in the NAD group, and the IL-18 levels were positively correlated with the IFN-γ and IL-6 levels. Anti-mouse IL-18-neutralizing monoclonal antibodies (anti-IL-18 nAb) inhibited angiotensin II-induced M1 macrophage differentiation and SMC apoptosis in vitro. IL-18 may participate in AD by regulating macrophage differentiation and macrophageinduced SMC apoptosis

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