Expression of Endothelin-1 in the Lungs of Patients with Pulmonary Hypertension

Adel Giaid, Masashi Yanagisawa, David Langleben, René P. Michel, Robert Levy, Hani Shennib, Sadao Kimura, Tomoh Masaki, William P. Duguid, Duncan J. Stewart

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Abstract

Background: Pulmonary hypertension is characterized by an increase in vascular tone or an abnormal proliferation of muscle cells in the walls of small pulmonary arteries. Endothelin-1 is a potent endothelium-derived vasoconstrictor peptide with important mitogenic properties. It has therefore been suggested that endothelin-1 may contribute to increases in pulmonary arterial tone or smooth-muscle proliferation in patients with pulmonary hypertension. We studied the sites and magnitude of endothelin-1 production in the lungs of patients with various causes of pulmonary hypertension. Methods: We studied the distribution of endothelin-1-like immunoreactivity (by immunocytochemical analysis) and endothelin-1 messenger RNA (by in situ hybridization) in lung specimens from 15 control subjects, 11 patients with plexogenic pulmonary arteriopathy (grades 4 through 6), and 17 patients with secondary pulmonary hypertension and pulmonary arteriopathy of grades 1 through 3. Results: In the controls, endothelin-1-like immunoreactivity was rarely seen in vascular endothelial cells. In the patients with pulmonary hypertension, endothelin-1-like immunoreactivity was abundant, predominantly in endothelial cells of pulmonary arteries with medial thickening and intimal fibrosis. Likewise, endothelin-1 messenger RNA was increased in the patients with pulmonary hypertension and was expressed primarily at sites of endothelin-1-like immunoreactivity. There was a strong correlation between the intensity of endothelin-1-like immunoreactivity and pulmonary vascular resistance in the patients with plexogenic pulmonary arteriopathy, but not in those with secondary pulmonary hypertension. Conclusions: Pulmonary hypertension is associated with the increased expression of endothelin-1 in vascular endothelial cells, suggesting that the local production of endothelin-1 may contribute to the vascular abnormalities associated with this disorder., Pulmonary hypertension is often a progressive condition, characterized by a relentless increase in pulmonary vascular resistance that ultimately leads to right-heart failure and death. Although the initiating factors may differ widely in patients with primary and various secondary causes of pulmonary hypertension, there may be common pathways of progression that reflect the limited range of vascular response to injury. Common to many forms of pulmonary hypertension is the proliferation of smooth-muscle cells in the vascular media and frequently the intima,1 triggered and perpetuated by as yet unknown mechanisms. The resulting intimal and medial thickening may reduce the caliber of resistance…

Original languageEnglish (US)
Pages (from-to)1732-1739
Number of pages8
JournalNew England Journal of Medicine
Volume328
Issue number24
DOIs
StatePublished - Jun 17 1993

ASJC Scopus subject areas

  • Medicine(all)

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    Giaid, A., Yanagisawa, M., Langleben, D., Michel, R. P., Levy, R., Shennib, H., Kimura, S., Masaki, T., Duguid, W. P., & Stewart, D. J. (1993). Expression of Endothelin-1 in the Lungs of Patients with Pulmonary Hypertension. New England Journal of Medicine, 328(24), 1732-1739. https://doi.org/10.1056/NEJM199306173282402