Persistence, re-expression, and induction of pulmonary arterial fibronectin, tropoelastin, and type I procollagen mRNA expression in neonatal hypoxic pulmonary hypertension

Anthony G. Durmowicz, William C. Parks, Dallas M. Hyde, Robert P. Mecham, Kurt R. Stenmark

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

Changes in the structure and function of muscular pulmonary arteries are crucial for normal adaptation to extrauterine life and rapid changes in matrix protein gene expression are likely necessary for this adaptation. We hypothesized that pathological stimuli imposed at the time of birth would alter developmental changes in matrix protein gene expression thereby affecting the normal post-uterine changes in pulmonary hemodynamics. We used in situ hybridization to examine the normal developmental expression of three extracellular matrix protein mRNAs, fibronectin, tropoelastin, and α1 (I) procollagen, in muscular pulmonary arteries of both fetal and neonatal calves and assessed the impact of severe hypoxia-induced pulmonary hypertension on their expression. Morphometric techniques were used to assess whether changes in matrix protein mRNA levels were related to changes in matrix fiber accumulation. Exposure to chronic hypoxia postnatally resulted in the persistence, reexpression, and induction of fibronectin, tropoelastin, and α1 (I) procollagen mRNAs, respectively, in muscular pulmonary arteries. In each case the hybridization signal was localized primarily to the adventitial layer of the vessel. Morphometric analysis showed that the increased hybridization signals seen correlated with an increase in both vascular elastin and collagen fiber volumes in the adventitial layer. We conclude that the change in expression of matrix genes in the pulmonary artery wall during exposure to chronic hypoxia is an important adaptive response to changes in hemodynamic factors and/or oxygen tension. The unchecked increase in matrix protein expression seen likely contributes to the pathological pulmonary arterial structural remodeling and loss of vasoreactivity that occurs during the development of severe neonatal pulmonary hypertension.

Original languageEnglish (US)
Pages (from-to)1411-1420
Number of pages10
JournalAmerican Journal of Pathology
Volume145
Issue number6
StatePublished - Dec 1994

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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