Effect of cGMP on lung microvascular endothelial barrier dysfunction following hydrogen peroxide

David B. Pearse; Larissa A. Shimoda; Alexander D. Verin; Natalia Bogatcheva; Cheil Moon; Gabriele V. Ronnett; Laura E. Welsh; Patrice M. Becker

doi:10.1080/10623320390272307

Effect of cGMP on lung microvascular endothelial barrier dysfunction following hydrogen peroxide

David B. Pearse, Larissa A. Shimoda, Alexander D. Verin, Natalia Bogatcheva, Cheil Moon, Gabriele V. Ronnett, Laura E. Welsh, Patrice M. Becker

Department of Brain Sciences

Johns Hopkins University

Research output: Contribution to journal › Article › peer-review

34 Scopus citations

Abstract

The authors determined the effect of cyclic guanosine 3′,5′-monophosphate (cGMP) on hydrogen peroxide (H₂O₂)-induced barrier dysfunction in bovine lung microvascular endothelial cell (BLMVEC) monolayers and compared the results to bovine pulmonary artery endothelial cells (BPAECs). In BLMVECs, H₂O₂ (250 μM) caused a 31.9% ± 4.8% decrease in transendothelial electrical resistance (TER) associated with increased actin stress fiber formation, intercellular gaps, and intracellular calcium concentration ([Ca²⁺]_i). The cGMP analogue 8-(p-chlorophenylthio)-cGMP (8p-CPT-cGMP; 30 or 50 μM) prevented the H₂O₂-induced decrease in TER (p < .001) as well as the cytoskeletal rearrangement and intercellular gap formation. 8-pCPT-cGMP (50 μM) attenuated the peak (418.8 ± 42.1 versus 665.2 ± 38.0 nmol/L; p < .001) and eliminated the sustained increase in [Ca²⁺]_i (193.5 ± 21.3 versus 418.8 ± 42.1 nmol/L; p < .001) caused by H₂O₂. 8-pCPT-cGMP also increased TER (14.2% ± 2.2%; p < .05) and decreased [Ca²⁺]_i (201.2 ± 12.5 vs. 214.4 ± 12.1 nmol/L; p < .03) before H₂O₂. In BPAECs, 8p-CPT-cGMP significantly attenuated H₂O₂-induced increases in permeability and [C²⁺]_i but less effectively than in BLMVECs. These results suggest that in BLMVECs, cGMP countered the adverse effects of H₂O₂ on barrier function by preventing actin cytoskeletal rearrangement and attenuating the increase in [Ca²⁺]_i.

Original language	English
Pages (from-to)	309-317
Number of pages	9
Journal	Endothelium: Journal of Endothelial Cell Research
Volume	10
Issue number	6
DOIs	https://doi.org/10.1080/10623320390272307
State	Published - 2003

Bibliographical note

Funding Information:
The authors thank Dr. James Sham for assistance with confocal microscopy and Diane Reese for excellent secretarial support. This work was supported by an Established Investigator Award (D. B. Pearse) and Scientific Development Grant (L. A. Shimoda) from the American Heart Association (funds contributed in part by the AHA, Maryland Affiliate) and National Heart, Lung, and Blood Institute grants HL-67189 (D. B. Pearse), HL-02933 (P. M. Becker), and HL-68062 (A. D. Verin).

Keywords

Calcium
Cytoskeleton
Pulmonary edema
cGMP-dependent protein kinases

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title = "Effect of cGMP on lung microvascular endothelial barrier dysfunction following hydrogen peroxide",

abstract = "The authors determined the effect of cyclic guanosine 3′,5′-monophosphate (cGMP) on hydrogen peroxide (H2O2)-induced barrier dysfunction in bovine lung microvascular endothelial cell (BLMVEC) monolayers and compared the results to bovine pulmonary artery endothelial cells (BPAECs). In BLMVECs, H2O2 (250 μM) caused a 31.9\% ± 4.8\% decrease in transendothelial electrical resistance (TER) associated with increased actin stress fiber formation, intercellular gaps, and intracellular calcium concentration ([Ca2+]i). The cGMP analogue 8-(p-chlorophenylthio)-cGMP (8p-CPT-cGMP; 30 or 50 μM) prevented the H2O2-induced decrease in TER (p < .001) as well as the cytoskeletal rearrangement and intercellular gap formation. 8-pCPT-cGMP (50 μM) attenuated the peak (418.8 ± 42.1 versus 665.2 ± 38.0 nmol/L; p < .001) and eliminated the sustained increase in [Ca2+]i (193.5 ± 21.3 versus 418.8 ± 42.1 nmol/L; p < .001) caused by H2O2. 8-pCPT-cGMP also increased TER (14.2\% ± 2.2\%; p < .05) and decreased [Ca2+]i (201.2 ± 12.5 vs. 214.4 ± 12.1 nmol/L; p < .03) before H2O2. In BPAECs, 8p-CPT-cGMP significantly attenuated H2O2-induced increases in permeability and [C2+]i but less effectively than in BLMVECs. These results suggest that in BLMVECs, cGMP countered the adverse effects of H2O2 on barrier function by preventing actin cytoskeletal rearrangement and attenuating the increase in [Ca2+]i.",

keywords = "Calcium, Cytoskeleton, Pulmonary edema, cGMP-dependent protein kinases",

author = "Pearse, \{David B.\} and Shimoda, \{Larissa A.\} and Verin, \{Alexander D.\} and Natalia Bogatcheva and Cheil Moon and Ronnett, \{Gabriele V.\} and Welsh, \{Laura E.\} and Becker, \{Patrice M.\}",

note = "Funding Information: The authors thank Dr. James Sham for assistance with confocal microscopy and Diane Reese for excellent secretarial support. This work was supported by an Established Investigator Award (D. B. Pearse) and Scientific Development Grant (L. A. Shimoda) from the American Heart Association (funds contributed in part by the AHA, Maryland Affiliate) and National Heart, Lung, and Blood Institute grants HL-67189 (D. B. Pearse), HL-02933 (P. M. Becker), and HL-68062 (A. D. Verin).",

year = "2003",

doi = "10.1080/10623320390272307",

language = "English",

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pages = "309--317",

journal = "Endothelium: Journal of Endothelial Cell Research",

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T1 - Effect of cGMP on lung microvascular endothelial barrier dysfunction following hydrogen peroxide

AU - Pearse, David B.

AU - Shimoda, Larissa A.

AU - Verin, Alexander D.

AU - Bogatcheva, Natalia

AU - Moon, Cheil

AU - Ronnett, Gabriele V.

AU - Welsh, Laura E.

AU - Becker, Patrice M.

N1 - Funding Information: The authors thank Dr. James Sham for assistance with confocal microscopy and Diane Reese for excellent secretarial support. This work was supported by an Established Investigator Award (D. B. Pearse) and Scientific Development Grant (L. A. Shimoda) from the American Heart Association (funds contributed in part by the AHA, Maryland Affiliate) and National Heart, Lung, and Blood Institute grants HL-67189 (D. B. Pearse), HL-02933 (P. M. Becker), and HL-68062 (A. D. Verin).

PY - 2003

Y1 - 2003

N2 - The authors determined the effect of cyclic guanosine 3′,5′-monophosphate (cGMP) on hydrogen peroxide (H2O2)-induced barrier dysfunction in bovine lung microvascular endothelial cell (BLMVEC) monolayers and compared the results to bovine pulmonary artery endothelial cells (BPAECs). In BLMVECs, H2O2 (250 μM) caused a 31.9% ± 4.8% decrease in transendothelial electrical resistance (TER) associated with increased actin stress fiber formation, intercellular gaps, and intracellular calcium concentration ([Ca2+]i). The cGMP analogue 8-(p-chlorophenylthio)-cGMP (8p-CPT-cGMP; 30 or 50 μM) prevented the H2O2-induced decrease in TER (p < .001) as well as the cytoskeletal rearrangement and intercellular gap formation. 8-pCPT-cGMP (50 μM) attenuated the peak (418.8 ± 42.1 versus 665.2 ± 38.0 nmol/L; p < .001) and eliminated the sustained increase in [Ca2+]i (193.5 ± 21.3 versus 418.8 ± 42.1 nmol/L; p < .001) caused by H2O2. 8-pCPT-cGMP also increased TER (14.2% ± 2.2%; p < .05) and decreased [Ca2+]i (201.2 ± 12.5 vs. 214.4 ± 12.1 nmol/L; p < .03) before H2O2. In BPAECs, 8p-CPT-cGMP significantly attenuated H2O2-induced increases in permeability and [C2+]i but less effectively than in BLMVECs. These results suggest that in BLMVECs, cGMP countered the adverse effects of H2O2 on barrier function by preventing actin cytoskeletal rearrangement and attenuating the increase in [Ca2+]i.

AB - The authors determined the effect of cyclic guanosine 3′,5′-monophosphate (cGMP) on hydrogen peroxide (H2O2)-induced barrier dysfunction in bovine lung microvascular endothelial cell (BLMVEC) monolayers and compared the results to bovine pulmonary artery endothelial cells (BPAECs). In BLMVECs, H2O2 (250 μM) caused a 31.9% ± 4.8% decrease in transendothelial electrical resistance (TER) associated with increased actin stress fiber formation, intercellular gaps, and intracellular calcium concentration ([Ca2+]i). The cGMP analogue 8-(p-chlorophenylthio)-cGMP (8p-CPT-cGMP; 30 or 50 μM) prevented the H2O2-induced decrease in TER (p < .001) as well as the cytoskeletal rearrangement and intercellular gap formation. 8-pCPT-cGMP (50 μM) attenuated the peak (418.8 ± 42.1 versus 665.2 ± 38.0 nmol/L; p < .001) and eliminated the sustained increase in [Ca2+]i (193.5 ± 21.3 versus 418.8 ± 42.1 nmol/L; p < .001) caused by H2O2. 8-pCPT-cGMP also increased TER (14.2% ± 2.2%; p < .05) and decreased [Ca2+]i (201.2 ± 12.5 vs. 214.4 ± 12.1 nmol/L; p < .03) before H2O2. In BPAECs, 8p-CPT-cGMP significantly attenuated H2O2-induced increases in permeability and [C2+]i but less effectively than in BLMVECs. These results suggest that in BLMVECs, cGMP countered the adverse effects of H2O2 on barrier function by preventing actin cytoskeletal rearrangement and attenuating the increase in [Ca2+]i.

KW - Calcium

KW - Cytoskeleton

KW - Pulmonary edema

KW - cGMP-dependent protein kinases

UR - https://www.scopus.com/pages/publications/1142263306

U2 - 10.1080/10623320390272307

DO - 10.1080/10623320390272307

M3 - Article

C2 - 14741846

AN - SCOPUS:1142263306

SN - 1062-3329

VL - 10

SP - 309

EP - 317

JO - Endothelium: Journal of Endothelial Cell Research

JF - Endothelium: Journal of Endothelial Cell Research

IS - 6

ER -

Effect of cGMP on lung microvascular endothelial barrier dysfunction following hydrogen peroxide

Abstract

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Keywords

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