Elevated NCX1 and NCKX4 expression in the patent postnatal ductus arteriosus of ductal-dependent congenital heart disease patients.

Abstract

Patency of the ductus arteriosus (DA) after birth is essential in ductal-dependent congenital heart disease. The Na(+)/Ca(2+) exchanger (NCX) has been demonstrated to play a key role in regulating vascular tone. The potassium-dependent Na(+)/Ca(2+) exchanger (NCKX) is a related family of NCX depending on the K(+) gradients which triggers DA constriction. The present study investigated the comparative expression of NCX and NCKX between a constricted DA and patent DA in human ductal-dependant congenital heart disease. Human DAs, which were patent (n = 10, age = 20.2 ± 4.3 days) or constricted (n = 10, age = 18.3 ± 3.9 days), were excised during surgery from neonates with ductal-dependent congenital heart disease. Western blotting analysis, real-time quantitative polymerase chain reaction analysis and immunofluorescence studies were performed to detect the protein and mRNA levels of NCX1, NCKX3, and NCKX4. The expressions of NCX1 and NCKX4 were significantly higher in the patent DA group at both the protein and mRNA levels, and expression was localized to the smooth muscle layer. These findings indicate that NCX1 and NCKX4 are up-regulated in human postnatal patent DAs and may represent potential therapeutic targets for maintaining DA patency in ductal-dependent congenital heart disease.