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. 1994 Mar;93(3):1234–1242. doi: 10.1172/JCI117077

Persistence of the fetal pattern of tropoelastin gene expression in severe neonatal bovine pulmonary hypertension.

K R Stenmark 1, A G Durmowicz 1, J D Roby 1, R P Mecham 1, W C Parks 1
PMCID: PMC294075  PMID: 8132763

Abstract

Neonatal hypoxic pulmonary hypertension causes increases and spatial changes in tropoelastin expression in pulmonary arteries. However, it is not clear if this is due to recruitment of quiescent smooth muscle cells (SMC) into an elastin-producing phenotype or persistence of the fetal pattern of tropoelastin gene expression. We evaluated the distribution and relative concentration of tropoelastin mRNA in intralobar pulmonary arteries from late gestation fetuses and in animals exposed to hypobaric hypoxia (430 mmHg) from birth for 1, 3, 7, or 14 d, as well as in age-matched and adult room air-breathing controls. In situ hybridization demonstrated that tropoelastin mRNA was distributed throughout the entire radius of the pulmonary vessel wall in the fetus and newborn calf. By 15 d of age, only cells in the inner third of the media expressed tropoelastin mRNA, and by adulthood no tropoelastin mRNA was detected in the vessel wall. These findings demonstrated that tropoelastin expression shuts off in a spatially specific pattern, moving from the abluminal to the luminal side of the medial in the neonatal pulmonary artery when pressures and resistance are falling. In the aorta of 15-d-old calves, tropoelastin mRNA expression was seen equally throughout the media, indicating tissue-specific regulation of elastin in the neonatal period. In contrast, intralobar pulmonary arteries from calves exposed to hypoxia, which prevented the normal postnatal decline in pulmonary artery pressure, maintained the fetal pattern and levels of tropoelastin mRNA expression at all time points. Thus, rather than causing a recruitment of SMC into an elastin-producing phenotype, neonatal pulmonary hypertension caused a persistence of the fetal pattern of tropoelastin expression in medial SMC. Cell-free translation showed that the same tropoelastin isoforms were made by mRNA from control and hypertensive calves and, unlike the ligamentum nuchae, did not change during the transition from fetal to neonatal life. We conclude that pulmonary hypertension in the neonate perturbs the normal postpartum repression of tropoelastin expression resulting in a persistence of the fetal spacial and isoform patterns of tropoelastin gene expression.

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Selected References

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