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Background: 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; in the DA, this increase causes functional closure, which is induced by smooth muscle contraction. Previous studies have demonstrated that hypoxia and/or oxygenation affect vascular remodeling. Therefore, we hypothesized that the rise in oxygen concentration would affect the vascular structure of the DA by producing proteins secreted from DA smooth muscle cells (SMCs). Method and Results: We performed LC-MS/MS analyses to comprehensively investigate the secreted proteins in the supernatants of rat DA SMCs that were harvested under a hypoxic condition (1% oxygen) or under a normoxic condition (21% oxygen). We found that the rise in oxygen concentration reduced the secretion of elastin from DA SMCs. Reverse transcriptionpolymerase chain reaction analyses also revealed that the expression levels of elastin mRNA were down-regulated in DA SMCs from a hypoxic to a normoxic condition. Conclusion: Our in vitro study demonstrated that the rise in oxygen concentration reduced the secretion of elastin. Because elastin forms internal elastic lamina and elastic fibers in the vascular muscle layers, this study suggests that the rise in blood oxygen concentration after birth reduces the secretion of elastin, which may play a role in DA structural remodeling after birth.

Oxygenation Decreases Elastin Secretion from Smooth Muscle Cells of the Rat Ductus Arteriosus