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

Nikolaos A. Maniatis, Irina V. Balyasnikova, Roman Metzger, Maricela Castellon, David J. Visintine, David E. Schwartz, Richard D. Minshall, Sergei M. Danilov*

*Corresponding author for this work

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 125I-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.

Original languageEnglish (US)
Pages (from-to)250-257
Number of pages8
JournalMicrovascular Research
Volume80
Issue number2
DOIs
StatePublished - Sep 1 2010

Fingerprint

Caveolin 1
Peptidyl-Dipeptidase A
Knockout Mice
Lung
Pulmonary Hypertension
Endothelial cells
Endothelial Cells
Blood Vessels
Cell signaling
Angiotensin I
Pulmonary diseases
Pulmonary Circulation
Enzyme activity
Angiotensin II
Pulmonary Artery
Lung Diseases
Homeostasis
Immunohistochemistry

Keywords

  • Anti-ACE monoclonal antibody
  • Endothelial dysfunction
  • Pulmonary hypertension

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

Cite this

Maniatis, N. A., Balyasnikova, I. V., Metzger, R., Castellon, M., Visintine, D. J., Schwartz, D. E., ... Danilov, S. M. (2010). Reduced expression of angiotensin I-converting enzyme in Caveolin-1 knockout mouse lungs. Microvascular Research, 80(2), 250-257. https://doi.org/10.1016/j.mvr.2010.04.008
Maniatis, Nikolaos A. ; Balyasnikova, Irina V. ; Metzger, Roman ; Castellon, Maricela ; Visintine, David J. ; Schwartz, David E. ; Minshall, Richard D. ; Danilov, Sergei M. / Reduced expression of angiotensin I-converting enzyme in Caveolin-1 knockout mouse lungs. In: Microvascular Research. 2010 ; Vol. 80, No. 2. pp. 250-257.
@article{74c4475e7e1a46c7bd4b4302976758df,
title = "Reduced expression of angiotensin I-converting enzyme in Caveolin-1 knockout mouse lungs",
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 125I-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.",
keywords = "Anti-ACE monoclonal antibody, Endothelial dysfunction, Pulmonary hypertension",
author = "Maniatis, {Nikolaos A.} and Balyasnikova, {Irina V.} and Roman Metzger and Maricela Castellon and Visintine, {David J.} and Schwartz, {David E.} and Minshall, {Richard D.} and Danilov, {Sergei M.}",
year = "2010",
month = "9",
day = "1",
doi = "10.1016/j.mvr.2010.04.008",
language = "English (US)",
volume = "80",
pages = "250--257",
journal = "Microvascular Research",
issn = "0026-2862",
publisher = "Academic Press Inc.",
number = "2",

}

Maniatis, NA, Balyasnikova, IV, Metzger, R, Castellon, M, Visintine, DJ, Schwartz, DE, Minshall, RD & Danilov, SM 2010, 'Reduced expression of angiotensin I-converting enzyme in Caveolin-1 knockout mouse lungs', Microvascular Research, vol. 80, no. 2, pp. 250-257. https://doi.org/10.1016/j.mvr.2010.04.008

Reduced expression of angiotensin I-converting enzyme in Caveolin-1 knockout mouse lungs. / Maniatis, Nikolaos A.; Balyasnikova, Irina V.; Metzger, Roman; Castellon, Maricela; Visintine, David J.; Schwartz, David E.; Minshall, Richard D.; Danilov, Sergei M.

In: Microvascular Research, Vol. 80, No. 2, 01.09.2010, p. 250-257.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Reduced expression of angiotensin I-converting enzyme in Caveolin-1 knockout mouse lungs

AU - Maniatis, Nikolaos A.

AU - Balyasnikova, Irina V.

AU - Metzger, Roman

AU - Castellon, Maricela

AU - Visintine, David J.

AU - Schwartz, David E.

AU - Minshall, Richard D.

AU - Danilov, Sergei M.

PY - 2010/9/1

Y1 - 2010/9/1

N2 - 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 125I-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.

AB - 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 125I-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.

KW - Anti-ACE monoclonal antibody

KW - Endothelial dysfunction

KW - Pulmonary hypertension

UR - http://www.scopus.com/inward/record.url?scp=77955412721&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955412721&partnerID=8YFLogxK

U2 - 10.1016/j.mvr.2010.04.008

DO - 10.1016/j.mvr.2010.04.008

M3 - Article

VL - 80

SP - 250

EP - 257

JO - Microvascular Research

JF - Microvascular Research

SN - 0026-2862

IS - 2

ER -