Involvement of the renin-angiotensin system in the progression of severe hand-foot-and-mouth disease

• Published in: PloS one 2018-05, Vol.13 (5), p.e0197861-e0197861
• Main Authors: Zhang, Chao, Chen, Shuaiyin, Zhou, Guangyuan, Jin, Yuefei, Zhang, Rongguang, Yang, Haiyan, Xi, Yuanlin, Ren, Jingchao, Duan, Guangcai
• Format: Article
• Language: English
• Subjects: Angiotensin; Angiotensin II; Biology and Life Sciences; Children; Coxsackievirus infections; Data processing; Development and progression; Dosage and administration; Drug therapy; Edema; Encephalitis; Enzyme-linked immunosorbent assay; Enzymes; Epidemiology; Hand-foot-and-mouth disease; Hypertension; Infants; Infections; Infectious diseases; Influenza; Kidney diseases; Lungs; Lysates; Medicine and Health Sciences; Meningitis; Mice; Muscles; Musculoskeletal system; Nervous system; Noradrenaline; Norepinephrine; Organs; Pathogenesis; Patients; Public health; Renin; Renin-angiotensin system; Research and Analysis Methods; Skeletal muscle; Systematic review; Viral infections
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0197861

Hand-foot-and-mouth disease (HFMD) is generally considered as a mild exanthematous disease to infants and young children worldwide. HFMD cases are usually mild and self-limiting but for few cases leads to complicated severe clinical outcomes, and even death. Previous studies have indicated that serum Ang II levels in patients with H7N9 infection were related to the severity of infection. However, the mechanisms underlying the pathogenesis of severe HFMD remain unclear. This study was undertaken to clarify the role of the renin-angiotensin system (RAS) in the progression of severe HFMD. In the present study, 162 children including HFMD patients and healthy controls were recruited. The data was analyzed by time-series fashion. Concentrations of angiotensin II (Ang II) and noradrenaline (NA) in serum of patients were measured with ELISA. We established a mouse model for enterovirus 71 (EV71) infection and determined concentrations of Ang II, NA in tissue lysates at 3, 5 and 7 days post infection (dpi). The concentrations of Ang II and NA in serum of the HFMD patients with mild or severe symptoms were significantly higher than that in healthy controls. Additionally, the concentrations of Ang II and NA in serum of severe cases were significantly higher than those mild cases and the increased concentrations of Ang II and NA showed the same time trend during the progression of HFMD in the severe cases. Furthermore, the concentrations of Ang II and NA in target organs of EV71-infected mice including brains, skeletal muscle, and lungs were increased with the progression of EV71 infection in mice. Histopathological alterations were observed in the brains, skeletal muscle and lungs of EV71-infected mice. Our study suggested that activation of the RAS is implicated in the pathogenesis of severe HFMD.