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Reduced expression of angiotensin I-converting enzyme in Caveolin-1 knockout mouse lungs

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Title: Reduced expression of angiotensin I-converting enzyme in Caveolin-1 knockout mouse lungs
Author(s): Maniatis, Nikolaos A.; Balyasnikova, Irina V.; Metzger, Roman; Castellon, Marciela; Visintine, David J.; Schwartz, David E.; Minshall, Richard D.; Danilov, Sergei M.
Subject(s): pulmonary hypertension endothelial dysfunction anti-ACE monoclonal antibody
Abstract: Reduced lung capillary expression of angiotensin I-converting enzyme (ACE), a key enzyme in cardiovascular pathophysiology, and of caveolin-1, an important regulator of endothelial cell signalling, has been demonstrated in various models of pulmonary arterial hypertension (PAH). We addressed the relationship between PAH and ACE expression in caveolin-1 knockout mice (Cav1(-/-)), which have moderate PAH. Tissue ACE activity was reduced by 50% in lungs from 3-month-old Cav1(-/-) mice compared to wild type (WT). A similar reduction in lung endothelial ACE expression was observed by measuring the lung uptake of I-125-labeled monoclonal anti-ACE antibody and by quantitative immunohistochemistry. These alterations in ACE are limited to capillary segments of the pulmonary circulation. Functionally, the increase in pulmonary artery pressure (PAP) in response to ACE conversion of angiotensin I to angiotensin II in isolated, perfused mouse lungs was reduced significantly in Cav1(-/-) mice compared to WT. Thus, these complementary approaches demonstrate the dependence of lung microvascular endothelial cell ACE protein expression on caveolin-1 expression and underscore the vital role of caveolin-1-regulated pulmonary vascular homeostasis on endothelial ACE expression and activity. In summary, we have revealed a novel role of caveolin-1 in the regulation of ACE expression in pulmonary capillary endothelial cells. Further understanding of the mechanism by which reduced caveolin-1 expression leads altered pulmonary vascular development, PAH, and reduced ACE expression may have important clinical implications in patients with these severe lung diseases.
Issue Date: 2010-09
Publisher: Elsevier
Citation Info: Maniatis, N. A., Balyasnikova, I. V., Metzger, R., Castellon, M., Visintine, D. J., Schwartz, D. E., Minshall, R. D., & Danilov, S. M. 2010. Reduced expression of angiotensin I-converting enzyme in Caveolin-1 knockout mouse lungs. Microvascular Research, 80(2): 250-257. DOI: 10.1016/j.mvr.2010.04.008
Type: Article
Description: Post print version of article may differ from published version. The definitive version is available through Elsevier at DOI: 10.1016/j.mvr.2010.04.008
URI: http://hdl.handle.net/10027/7363
ISSN: 0026-2862
Date Available in INDIGO: 2011-03-01
 

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