Citations to this article

Regional variability in preproEndothelin-1 gene expression in sheep pulmonary artery and lung during the onset of air-induced chronic pulmonary hypertension. Participation Of arterial smooth muscle cells.
E Tchekneva, … , M L Lawrence, B Meyrick
E Tchekneva, … , M L Lawrence, B Meyrick
Published March 15, 1998
Citation Information: J Clin Invest. 1998;101(6):1389-1397. https://doi.org/10.1172/JCI622.
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Research Article

Regional variability in preproEndothelin-1 gene expression in sheep pulmonary artery and lung during the onset of air-induced chronic pulmonary hypertension. Participation Of arterial smooth muscle cells.

Abstract

We investigated preproendothelin-1 (ppET-1) gene expression in the main and midregion pulmonary artery, and peripheral lung from control sheep and from animals during the development of the structural and functional changes of air-induced chronic pulmonary hypertension (CPH). Measurement of ET-1 in lung lymph (n = 7) at 1, 4, 8, and 12 d of continuous air embolization (CAE) showed a significant increase from day 4 compared with controls (n = 4). A semiquantitative reverse transcription PCR for ppET-1 gene expression was developed using ovine-specific primers. Control sheep showed strikingly fewer ppET-1 transcripts in the midregion (22.9+/-2.3 ng cDNA equivalents) than in the main pulmonary artery and lung (736.0+/-263.7 and 705.5+/-125.7, respectively). Smooth muscle cells (SMC) isolated from the main and midregion artery of control sheep confirmed these findings and showed higher levels of intracellular ET-1 synthesis in the main versus the midregion artery. Differences in gene expression persisted during CAE. In main pulmonary artery and lung, ppET-1 transcripts fell to < 1% of controls. However, transcripts in the midregion artery showed a gradual increase. Coincubation of SMC from the midregion with ET-1 plus TGF-beta resulted in an increase in intracellular big ET-1 and a decrease in SMC from the main artery. We conclude that SMC from the main and midregion pulmonary artery are phenotypically different and suggest that local synthesis of ET-1 and TGF-beta, and increased levels of ET-1 in lung lymph, regulate ppET-1 gene expression and synthesis in arterial SMC during the development of air-induced CPH.

Authors

E Tchekneva, T Quertermous, B W Christman, M L Lawrence, B Meyrick

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Citations to this article (17)

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SJ Wort, M Ito, PC Chou, SK Master, R Badiger, E Jazrawi, P Souza, TW Evans, JA Mitchell, L Pinhu, K Ito, IM Adcock 		The Journal of biological chemistry 2009
Endothelin receptor antagonists in preclinical models of pulmonary hypertension
SS Pullamsetti, RT Schermuly 		European Journal of Clinical Investigation 2009
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Lung Biology in Health and Disease: Cellular and Molecular Mechanisms
E Sapey, R Stockley 		Lung Biology in Health and Disease: Experimental Models and Therapeutic Potential 2005
The endothelin system in pulmonary hypertension
RP Michel, D Langleben, J Dupuis 		Canadian Journal of Physiology and Pharmacology 2003
Cyclooxygenase is regulated by ET-1 and MAPKs in peripheral lung microvascular smooth muscle cells
D Chen, EV Balyakina, M Lawrence, BW Christman, B Meyrick 		American journal of physiology. Lung cellular and molecular physiology 2003
ET-1 receptor gene expression and distribution in L1 and L2 cells from hypertensive sheep pulmonary artery
EV Balyakina, D Chen, ML Lawrence, S Manning, RE Parker, SB Shappell, B Meyrick 		American journal of physiology. Lung cellular and molecular physiology 2002
Cyclooxygenase-2 Acts as an Endogenous Brake on Endothelin-1 Release by Human Pulmonary Artery Smooth Muscle Cells: Implications for Pulmonary Hypertension
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THE PATHOLOGY OF PULMONARY ARTERY HYPERTENSION
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D Lepailleur-Enouf, O Valdenaire, M Philippe, M Jandrot-Perrus, JB Michel 		American journal of physiology. Heart and circulatory physiology 2000
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