Expression of leptin and its receptor correlates with hypoxia- inducible factor-1α in infants with cyanotic congenital heart disease

Abstract

Objective To investigate the correlation between serum leptin level and body mass index (BMI) in infants with cyanosis congenital heart disease, and the relationship between leptin and Ob gene receptor (Ob-R) and hypoxia-inducible factor 1α (HIF-1α) in myocardium. Methods A total of 52 children under 6 months of age with congenital heart disease who underwent surgical treatment in the Department of Congenital Heart Surgery, Fuwai Hospital from January 2019 to October 2020 were included in this study. According to the arterial partial pressure of oxygen (PaO2) of 90 mmHg, they were divided into cyanotic group (n=30) and acyanotic group (n=22). Their height and weight were collected to calculate BMI. The serum leptin level was measured by ELISA. The expressions of HIF-1α and Ob-R in myocardial tissue were detected by RT-PCR and Western blot. In animal model, SD rats were divided into normoxia group and hypoxia intervention group, which were subjected to continuous hypoxia (10% O2) for 4 weeks. The hypoxia intervention group received intraperitoneal injection of HIF-1α inhibitor digoxin (2 mg/kg) daily from the 14 th to 21st day of hypoxia, respectively. The body weight of rats was recorded, and the expressions of HIF-1α and Ob-R were detected by RT-qPCR and Western blot. Results Compared with the acyanosis group, the cyanosis group had a significantly lower BMI (P＜0.05) and a lower leptin/BMI ratio (leptin /BMI) (P＜0.05). Spearman correlation analysis confirmed that serum leptin in the circulatory system was positively correlated with BMI (P＜0.05). In the cyanosis group, the expression of Ob-R increased with the upregulation of HIF-1α,showing a positive correlation. In animal model, with the down-regulation of HIF-1α expression in digoxin injection, the Ob-R level was significantly lower than that in the control group(P＜0.05), the trend of weight loss was significantly inhibited(P＜0.05). The right ventricular hypertrophy index was significantly lower than that in the control group (P＜0.05). Conclusions HIF-1α regulates the expression of Ob-R in myocardial tissue, and the mechanism of its association with leptin and Ob-R may help to find new therapeutic target for improving the prognosis of infants with congenital heart disease.

Keywords

• congenital heart disease|leptin|ob gene receptor|hypoxia-inducible factor 1α