mortality/aging
• homozygotes die within 12-48 hours after birth
• administration of indomethacin, which inhibits PGE2 production, rescues neonatal lethality and ductus arteriosus patency
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cardiovascular system
• newborn homozygotes fail to exhibit remodeling of the ductus arteriosus i.e. lifting of endothelial cells, fragmentation of elastic lamina, migration of smooth-muscle cells and obstruction of lumen by intimal thickening
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• newborn homozygotes exhibit a patent ductus arteriosus of a similar diameter to that of a full-term fetus
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• newborn homozygotes die of congestive heart failure as a result of left-ventricle overload and exposure of the right ventricle to arterial pressures
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homeostasis/metabolism
• newborn homozygotes exhibit significantly increased PGE2 levels; in contrast, TxB2 levels remain normal
• perinatal PGE2 levels remain abnormally elevated, intracellular cAMP levels do not change, and DA remodeling is inhibited
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cellular
• newborn homozygotes fail to exhibit remodeling of the ductus arteriosus i.e. lifting of endothelial cells, fragmentation of elastic lamina, migration of smooth-muscle cells and obstruction of lumen by intimal thickening
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• newborn homozygotes exhibit a patent ductus arteriosus of a similar diameter to that of a full-term fetus
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