Adipose tissue hypoxia caused by cyanotic congenital heart disease and its impact on adipokine dysregulation

Objective: To investigate the effects of hypoxia induced by CCHD on the expression and secretion of adipokines. Methods: Subcutaneous adipose tissue and serum were obtained from elective cardiac surgery patients. In CCHD group, n = 17; and in ACHD (Acyanosis congenital heart disease) group, n = 15. Vascular endothelial growth factor (VEGF), inflammation-related adipokines, adiponectin (APN) and Endoplasmic reticulum stress (ER stress) markers were measured in mRNA levels. Hypoxia inducible factor 1α (HIF-1α) and ER stress markers were also measured in protein levels. Results: Immunohistochemical staining showed that protein expression level of VEGF was markedly increased relative to acyanotic groups. Adipose tissue was hypoxic in cyanotic groups. Adipose tissue hypoxia (ATH) led to a substantial increase in inflammation-related adipokines, and a remarkable reduction in adiponectin mRNA levels. Endoplasmic reticulum stress markers were activated by hypoxia. ER stress has been linked to inflammation. These changes were partially reversed by the intervention of normoxia. We exposed normal adipose tissue to CoCl2, a hypoxia mimic, and achieved results similar to the CCHD group. Conclusions: Adipose tissue in CCHD is hypoxic. The change of adiponectin and inflammation-related adipokines are partially caused by ER stress.