Developmental changes in prostacyclin synthesis are conserved in cultured pulmonary endothelium and vascular smooth muscle

Philip W. Shaul, Margaret C. Pace, Zhong Chen, Timothy S. Brannon

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17 Citations (Scopus)

Abstract

Prostacyclin (PGI2) is a key mediator of pulmonary vascular and parenchymal function during late fetal and early postnatal life, and its synthesis in intrapulmonary arteries increases markedly during that period. The rate-limiting enzyme in PGI2 synthesis in the developing lung is cyclooxygenase (COX). To understand better the mechanisms underlying the developmental increase in PGI2 synthesis, we evaluated PGI2 production in early-passage, cultured pulmonary artery endothelial cells (PAEC) and pulmonary vascular smooth-muscle cells (VSM) from fetal and newborn lambs. In arterial segments, PGI2 synthesis was sevenfold greater in intact arteries from newborn than from fetal lambs, and it was 12-fold greater in endothelium-denuded newborn than in fetal arteries, indicating that the developmental increase occurs in both the endothelium and medial layer. Similarly, basal PGI2 production was three-fold greater in newborn than in fetal PAEC, and 2.5-fold greater in newborn than in fetal pulmonary VSM cells. Calcium ionophore (A23187)-stimulated and arachidonic acid-stimulated PGI2 synthesis were also greater in newborn than in fetal PAEC and VSM, revealing a developmental upregulation in COX enzymatic activity in both cell types. Immunoblot analysis showed that this is due to greater COX-1 protein expression in newborn than in fetal vascular cells; COX-2 protein expression was not detected. In addition, COX-1 messenger RNA (mRNA) abundance was greater in newborn than in fetal PAEC, and this was not due to a difference in COX-1 mRNA stability. Thus, the developmental upregulation of PGI2 synthesis is conserved in early-passage PAEC and pulmonary VSM, and is related to a maturational increase in COX-1 gene expression. Further studies with the cultured cell model will enable determination of the factors that directly regulate COX-1 expression in the developing pulmonary vasculature.

Original languageEnglish (US)
Pages (from-to)113-121
Number of pages9
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume20
Issue number1
StatePublished - 1999

Fingerprint

Epoprostenol
Vascular Smooth Muscle
Endothelium
Muscle
Cyclooxygenase 1
Lung
Endothelial cells
Pulmonary Artery
Endothelial Cells
Smooth Muscle Myocytes
Arteries
Prostaglandin-Endoperoxide Synthases
Blood Vessels
Up-Regulation
Cells
Messenger RNA
Calcium Ionophores
RNA Stability
Calcimycin
Cyclooxygenase 2

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Pulmonary and Respiratory Medicine

Cite this

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title = "Developmental changes in prostacyclin synthesis are conserved in cultured pulmonary endothelium and vascular smooth muscle",
abstract = "Prostacyclin (PGI2) is a key mediator of pulmonary vascular and parenchymal function during late fetal and early postnatal life, and its synthesis in intrapulmonary arteries increases markedly during that period. The rate-limiting enzyme in PGI2 synthesis in the developing lung is cyclooxygenase (COX). To understand better the mechanisms underlying the developmental increase in PGI2 synthesis, we evaluated PGI2 production in early-passage, cultured pulmonary artery endothelial cells (PAEC) and pulmonary vascular smooth-muscle cells (VSM) from fetal and newborn lambs. In arterial segments, PGI2 synthesis was sevenfold greater in intact arteries from newborn than from fetal lambs, and it was 12-fold greater in endothelium-denuded newborn than in fetal arteries, indicating that the developmental increase occurs in both the endothelium and medial layer. Similarly, basal PGI2 production was three-fold greater in newborn than in fetal PAEC, and 2.5-fold greater in newborn than in fetal pulmonary VSM cells. Calcium ionophore (A23187)-stimulated and arachidonic acid-stimulated PGI2 synthesis were also greater in newborn than in fetal PAEC and VSM, revealing a developmental upregulation in COX enzymatic activity in both cell types. Immunoblot analysis showed that this is due to greater COX-1 protein expression in newborn than in fetal vascular cells; COX-2 protein expression was not detected. In addition, COX-1 messenger RNA (mRNA) abundance was greater in newborn than in fetal PAEC, and this was not due to a difference in COX-1 mRNA stability. Thus, the developmental upregulation of PGI2 synthesis is conserved in early-passage PAEC and pulmonary VSM, and is related to a maturational increase in COX-1 gene expression. Further studies with the cultured cell model will enable determination of the factors that directly regulate COX-1 expression in the developing pulmonary vasculature.",
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AU - Pace, Margaret C.

AU - Chen, Zhong

AU - Brannon, Timothy S.

PY - 1999

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N2 - Prostacyclin (PGI2) is a key mediator of pulmonary vascular and parenchymal function during late fetal and early postnatal life, and its synthesis in intrapulmonary arteries increases markedly during that period. The rate-limiting enzyme in PGI2 synthesis in the developing lung is cyclooxygenase (COX). To understand better the mechanisms underlying the developmental increase in PGI2 synthesis, we evaluated PGI2 production in early-passage, cultured pulmonary artery endothelial cells (PAEC) and pulmonary vascular smooth-muscle cells (VSM) from fetal and newborn lambs. In arterial segments, PGI2 synthesis was sevenfold greater in intact arteries from newborn than from fetal lambs, and it was 12-fold greater in endothelium-denuded newborn than in fetal arteries, indicating that the developmental increase occurs in both the endothelium and medial layer. Similarly, basal PGI2 production was three-fold greater in newborn than in fetal PAEC, and 2.5-fold greater in newborn than in fetal pulmonary VSM cells. Calcium ionophore (A23187)-stimulated and arachidonic acid-stimulated PGI2 synthesis were also greater in newborn than in fetal PAEC and VSM, revealing a developmental upregulation in COX enzymatic activity in both cell types. Immunoblot analysis showed that this is due to greater COX-1 protein expression in newborn than in fetal vascular cells; COX-2 protein expression was not detected. In addition, COX-1 messenger RNA (mRNA) abundance was greater in newborn than in fetal PAEC, and this was not due to a difference in COX-1 mRNA stability. Thus, the developmental upregulation of PGI2 synthesis is conserved in early-passage PAEC and pulmonary VSM, and is related to a maturational increase in COX-1 gene expression. Further studies with the cultured cell model will enable determination of the factors that directly regulate COX-1 expression in the developing pulmonary vasculature.

AB - Prostacyclin (PGI2) is a key mediator of pulmonary vascular and parenchymal function during late fetal and early postnatal life, and its synthesis in intrapulmonary arteries increases markedly during that period. The rate-limiting enzyme in PGI2 synthesis in the developing lung is cyclooxygenase (COX). To understand better the mechanisms underlying the developmental increase in PGI2 synthesis, we evaluated PGI2 production in early-passage, cultured pulmonary artery endothelial cells (PAEC) and pulmonary vascular smooth-muscle cells (VSM) from fetal and newborn lambs. In arterial segments, PGI2 synthesis was sevenfold greater in intact arteries from newborn than from fetal lambs, and it was 12-fold greater in endothelium-denuded newborn than in fetal arteries, indicating that the developmental increase occurs in both the endothelium and medial layer. Similarly, basal PGI2 production was three-fold greater in newborn than in fetal PAEC, and 2.5-fold greater in newborn than in fetal pulmonary VSM cells. Calcium ionophore (A23187)-stimulated and arachidonic acid-stimulated PGI2 synthesis were also greater in newborn than in fetal PAEC and VSM, revealing a developmental upregulation in COX enzymatic activity in both cell types. Immunoblot analysis showed that this is due to greater COX-1 protein expression in newborn than in fetal vascular cells; COX-2 protein expression was not detected. In addition, COX-1 messenger RNA (mRNA) abundance was greater in newborn than in fetal PAEC, and this was not due to a difference in COX-1 mRNA stability. Thus, the developmental upregulation of PGI2 synthesis is conserved in early-passage PAEC and pulmonary VSM, and is related to a maturational increase in COX-1 gene expression. Further studies with the cultured cell model will enable determination of the factors that directly regulate COX-1 expression in the developing pulmonary vasculature.

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