Apoptosis in the Human Neonatal Vascular Remodeling

Hwang, Kyung Kuk; Kim, Hyo Soo; Seo, Jung Uk; Chae, In Ho; Kim, Chul Ho; Sohn, Dae Won; Oh, Byung Hee; Lee, Myoung Mook; Park, Young Bae; Choi, Yun Shik; Lee, Young Woo

Abstract

BACKGROUND AND OBJECTIVES
In order to verify that apoptosis is one of the possible mechanisms of human neonatal vascular remodeling during transition from fetal to neonatal circulation, we identified apoptosis and analyzed its mechanism by evaluating apoptosis-related genes in umbilical vessel versus ascending aorta, ductus arteriosus (DA) versus adjacent pulmonary artery and aorta, and aorta versus its branching arteries.
MATERIALS AND METHODS
Twenty-two umbilical cords, six ductus arteriosus with adjacent aortae and pulmonary arteries, and four aortic arches with their branching great arteries, were obtained from neonates. The presence of apoptotic cells was demonstrated by electron microscopy (EM) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). Immunohistochemical staining and Western blotting were used for the analysis of the proteins of apoptosis-related gene.
RESULTS
Apoptosis of the smooth muscle cells of the umbilical vessels were identified in all UC, which were examined by electron microscopy and TUNEL. The expressions of Bax and Bcl-X were shown by immunohistochemistry to be stronger in umbilical artery than in the neonatal aorta, but Bcl-2 was weak in both arteries. In the immunoblot analysis of UC, the expression of the proapoptotic short isoform of Bcl-X was stronger than in other tissue, and caspase-3 was selectively activated whereas it was not in the other components of the cardiovascular system. However, the expression patterns of the Fas Ag and Fas ligand (i.e. positive Fas Ag and negative Fas ligand), were similar in umbilical artery and aorta. This Bax-associated apoptosis was also observed in other vascular sites which undergo dramatic hemodynamic changes during birth, such as, the ductus arteriosus and the branching points of the great arteries from the aortic arch.
CONCLUSIONS
Apoptosis is involved in the closure and regression of human umbilical vessels and the ductus arteriosus and in the remodeling of the branching great arteries during the neonatal period, where the Bax/Bcl-2/Bcl-X system, not Fas Ag/Fas ligand system, is likely to play a key role.