| Copper-dependence of Angioproliferation in Pulmonary Arterial Hypertension in Rats and Humans. | |
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MedLine Citation:
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PMID: 22162909 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Rationale: Vascular lumen obliteration by endothelial cell growth is a hallmark of many forms of severe pulmonary arterial hypertension. Copper plays a significant role in the control of endothelial cell proliferation in cancer and wound healing. Objective: To determine whether angioproliferation in rats with experimental pulmonary arterial hypertension and human pulmonary microvascular endothelial cell proliferation depend on the proangiogenic action of copper. Measurements, methods and main results: A copper depleted diet prevented, and copper chelation with tetrathiomolybdate reversed the development of severe experimental pulmonary arterial hypertension. Copper chelation induced reopening of obliterated vessels was caused by caspase-independent apoptosis, reduced vessel wall cell proliferation and a normalization of the vessel wall structure. No evidence was found in favor of a role of super oxide 1 inhibition or lysyl-oxidase 1 inhibition in the reversal of angioproliferation. Tetrathiomolybdate inhibited the proliferation of human pulmonary microvascular endothelial cells isolated from explanted lungs from control subjects and patients with pulmonary arterial hypertension. Conclusions: These data suggest that inhibition of endothelial cell proliferation by a copper restricting strategy could be explored as a new therapeutic approach in pulmonary arterial hypertension. It remains to be determined, however, whether with anti-angiogenic treatment in patients with pulmonary arterial hypertension, potential toxicity to the right ventricle is offset by the beneficial pulmonary vascular effects. |
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Authors:
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Harm J Bogaard; Shiro Mizuno; Christophe Guignabert; Aysar A Al Hussaini; Daniela Farkas; Gerrina Ruiter; Donatas Kraskauskas; Elie Fadel; Jeremy C Allegood; Marc Humbert; Anton Vonk Noordegraaf; Sarah Spiegel; Laszlo Farkas; Norbert F Voelkel |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-8 |
Journal Detail:
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Title: American journal of respiratory cell and molecular biology Volume: - ISSN: 1535-4989 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8917225 Medline TA: Am J Respir Cell Mol Biol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Division of Pulmonary & Critical Care Medicine and Victoria Johnson Center for Lung Research, Virginia Commonwealth University, School of Medicine, Richmond, Virginia, United States; Department of Pulmonary Medicine, VU University Medical Center, Amsterdam, Netherlands. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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