Kawakami Shoji, Minamisawa Susumu
Department of Life Science and Medical Bioscience, Waseda University, Tokyo, Japan.
Department of Cell Physiology, Jikei University, Tokyo, Japan.
Pediatr Int. 2015 Aug;57(4):541-5. doi: 10.1111/ped.12684.
The ductus arteriosus (DA), a fetal arterial connection between the main pulmonary artery and the descending aorta, normally closes immediately after birth. The oxygen concentration in the blood rises after birth, and in the DA this increase in oxygen concentration causes functional closure, which is induced by smooth muscle contraction. Previous studies have demonstrated that hypoxia and/or oxygenation affect vascular remodeling of various vessels. Therefore, we hypothesized that the rise in oxygen concentration would affect the vascular structure of the DA due to production of proteins secreted from DA smooth muscle cells (SMC).
Liquid chromatography-tandem mass spectrometry was used to comprehensively investigate the secreted proteins in the supernatant of rat DA SMC harvested under hypoxic conditions (1% oxygen) or under normoxic conditions (21% oxygen). We found that the rise in oxygen concentration reduced the secretion of elastin from DA SMC. On reverse transcription-polymerase chain reaction, the expression of elastin mRNA was not significantly changed in DA SMC from hypoxic to normoxic conditions.
Given that elastin forms internal elastic lamina and elastic fibers in the vascular muscle layers, and that a rise in oxygen concentration reduced the secretion of elastin, this suggests that the rise in blood oxygen concentration after birth reduces the secretion of elastin, and therefore may play a role in DA structural remodeling after birth.
动脉导管(DA)是胎儿期主肺动脉与降主动脉之间的动脉连接,通常在出生后立即关闭。出生后血液中的氧浓度升高,在动脉导管中,这种氧浓度的升高会导致功能性关闭,这是由平滑肌收缩引起的。先前的研究表明,缺氧和/或氧合会影响各种血管的血管重塑。因此,我们推测氧浓度的升高会由于动脉导管平滑肌细胞(SMC)分泌的蛋白质的产生而影响动脉导管的血管结构。
采用液相色谱-串联质谱法全面研究在缺氧条件(1%氧气)或常氧条件(21%氧气)下收获的大鼠动脉导管平滑肌细胞上清液中的分泌蛋白。我们发现氧浓度的升高会减少动脉导管平滑肌细胞中弹性蛋白的分泌。在逆转录-聚合酶链反应中,从缺氧条件到常氧条件,动脉导管平滑肌细胞中弹性蛋白mRNA的表达没有显著变化。
鉴于弹性蛋白在血管肌层中形成内弹性膜和弹性纤维,且氧浓度的升高会减少弹性蛋白的分泌,这表明出生后血氧浓度的升高会减少弹性蛋白的分泌,因此可能在出生后动脉导管的结构重塑中起作用。