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Glutathione peroxidase-1 deficiency potentiates dysregulatory modifications of endothelial nitric oxide synthase and vascular dysfunction in aging

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Glutathione peroxidase-1 deficiency potentiates dysregulatory modifications of endothelial nitric oxide synthase and vascular dysfunction in aging. / Oelze, Matthias; Kröller-Schön, Swenja; Steven, Sebastian; Lubos, Edith; Doppler, Christopher; Hausding, Michael; Tobias, Silke; Brochhausen, Christoph; Li, Huige; Torzewski, Michael; Wenzel, Philip; Bachschmid, Markus; Lackner, Karl J; Schulz, Eberhard; Münzel, Thomas; Daiber, Andreas.

In: HYPERTENSION, Vol. 63, No. 2, 02.2014, p. 390-396.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Oelze, M, Kröller-Schön, S, Steven, S, Lubos, E, Doppler, C, Hausding, M, Tobias, S, Brochhausen, C, Li, H, Torzewski, M, Wenzel, P, Bachschmid, M, Lackner, KJ, Schulz, E, Münzel, T & Daiber, A 2014, 'Glutathione peroxidase-1 deficiency potentiates dysregulatory modifications of endothelial nitric oxide synthase and vascular dysfunction in aging', HYPERTENSION, vol. 63, no. 2, pp. 390-396. https://doi.org/10.1161/HYPERTENSIONAHA.113.01602

APA

Oelze, M., Kröller-Schön, S., Steven, S., Lubos, E., Doppler, C., Hausding, M., Tobias, S., Brochhausen, C., Li, H., Torzewski, M., Wenzel, P., Bachschmid, M., Lackner, K. J., Schulz, E., Münzel, T., & Daiber, A. (2014). Glutathione peroxidase-1 deficiency potentiates dysregulatory modifications of endothelial nitric oxide synthase and vascular dysfunction in aging. HYPERTENSION, 63(2), 390-396. https://doi.org/10.1161/HYPERTENSIONAHA.113.01602

Vancouver

Oelze M, Kröller-Schön S, Steven S, Lubos E, Doppler C, Hausding M et al. Glutathione peroxidase-1 deficiency potentiates dysregulatory modifications of endothelial nitric oxide synthase and vascular dysfunction in aging. HYPERTENSION. 2014 Feb;63(2):390-396. https://doi.org/10.1161/HYPERTENSIONAHA.113.01602

Bibtex

@article{5771dbadf2bf4885966fad7263257363,
title = "Glutathione peroxidase-1 deficiency potentiates dysregulatory modifications of endothelial nitric oxide synthase and vascular dysfunction in aging",
abstract = "Recently, we demonstrated that gene ablation of mitochondrial manganese superoxide dismutase and aldehyde dehydrogenase-2 markedly contributed to age-related vascular dysfunction and mitochondrial oxidative stress. The present study has sought to investigate the extent of vascular dysfunction and oxidant formation in glutathione peroxidase-1-deficient (GPx-1(-/-)) mice during the aging process with special emphasis on dysregulation (uncoupling) of the endothelial NO synthase. GPx-1(-/-) mice on a C57 black 6 (C57BL/6) background at 2, 6, and 12 months of age were used. Vascular function was significantly impaired in 12-month-old GPx-1(-/-) -mice as compared with age-matched controls. Oxidant formation, detected by 3-nitrotyrosine staining and dihydroethidine-based fluorescence microtopography, was increased in the aged GPx-1(-/-) mice. Aging per se caused a substantial protein kinase C- and protein tyrosine kinase-dependent phosphorylation as well as S-glutathionylation of endothelial NO synthase associated with uncoupling, a phenomenon that was more pronounced in aged GPx-1(-/-) mice. GPx-1 ablation increased adhesion of leukocytes to cultured endothelial cells and CD68 and F4/80 staining in cardiac tissue. Aged GPx-1(-/-) mice displayed increased oxidant formation as compared with their wild-type littermates, triggering redox-signaling pathways associated with endothelial NO synthase dysfunction and uncoupling. Thus, our data demonstrate that aging leads to decreased NO bioavailability because of endothelial NO synthase dysfunction and uncoupling of the enzyme leading to endothelial dysfunction, vascular remodeling, and promotion of adhesion and infiltration of leukocytes into cardiovascular tissue, all of which was more prominent in aged GPx-1(-/-) mice. ",
keywords = "Aged, Aging/metabolism, Animals, Cells, Cultured, Endothelial Cells/cytology, Endothelium, Vascular/metabolism, Glutathione Peroxidase/deficiency, Humans, Leukocytes/cytology, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Nitric Oxide Synthase Type III/metabolism, Oxidants/metabolism, Oxidative Stress/physiology, Phosphorylation/physiology",
author = "Matthias Oelze and Swenja Kr{\"o}ller-Sch{\"o}n and Sebastian Steven and Edith Lubos and Christopher Doppler and Michael Hausding and Silke Tobias and Christoph Brochhausen and Huige Li and Michael Torzewski and Philip Wenzel and Markus Bachschmid and Lackner, {Karl J} and Eberhard Schulz and Thomas M{\"u}nzel and Andreas Daiber",
year = "2014",
month = feb,
doi = "10.1161/HYPERTENSIONAHA.113.01602",
language = "English",
volume = "63",
pages = "390--396",
journal = "HYPERTENSION",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

RIS

TY - JOUR

T1 - Glutathione peroxidase-1 deficiency potentiates dysregulatory modifications of endothelial nitric oxide synthase and vascular dysfunction in aging

AU - Oelze, Matthias

AU - Kröller-Schön, Swenja

AU - Steven, Sebastian

AU - Lubos, Edith

AU - Doppler, Christopher

AU - Hausding, Michael

AU - Tobias, Silke

AU - Brochhausen, Christoph

AU - Li, Huige

AU - Torzewski, Michael

AU - Wenzel, Philip

AU - Bachschmid, Markus

AU - Lackner, Karl J

AU - Schulz, Eberhard

AU - Münzel, Thomas

AU - Daiber, Andreas

PY - 2014/2

Y1 - 2014/2

N2 - Recently, we demonstrated that gene ablation of mitochondrial manganese superoxide dismutase and aldehyde dehydrogenase-2 markedly contributed to age-related vascular dysfunction and mitochondrial oxidative stress. The present study has sought to investigate the extent of vascular dysfunction and oxidant formation in glutathione peroxidase-1-deficient (GPx-1(-/-)) mice during the aging process with special emphasis on dysregulation (uncoupling) of the endothelial NO synthase. GPx-1(-/-) mice on a C57 black 6 (C57BL/6) background at 2, 6, and 12 months of age were used. Vascular function was significantly impaired in 12-month-old GPx-1(-/-) -mice as compared with age-matched controls. Oxidant formation, detected by 3-nitrotyrosine staining and dihydroethidine-based fluorescence microtopography, was increased in the aged GPx-1(-/-) mice. Aging per se caused a substantial protein kinase C- and protein tyrosine kinase-dependent phosphorylation as well as S-glutathionylation of endothelial NO synthase associated with uncoupling, a phenomenon that was more pronounced in aged GPx-1(-/-) mice. GPx-1 ablation increased adhesion of leukocytes to cultured endothelial cells and CD68 and F4/80 staining in cardiac tissue. Aged GPx-1(-/-) mice displayed increased oxidant formation as compared with their wild-type littermates, triggering redox-signaling pathways associated with endothelial NO synthase dysfunction and uncoupling. Thus, our data demonstrate that aging leads to decreased NO bioavailability because of endothelial NO synthase dysfunction and uncoupling of the enzyme leading to endothelial dysfunction, vascular remodeling, and promotion of adhesion and infiltration of leukocytes into cardiovascular tissue, all of which was more prominent in aged GPx-1(-/-) mice.

AB - Recently, we demonstrated that gene ablation of mitochondrial manganese superoxide dismutase and aldehyde dehydrogenase-2 markedly contributed to age-related vascular dysfunction and mitochondrial oxidative stress. The present study has sought to investigate the extent of vascular dysfunction and oxidant formation in glutathione peroxidase-1-deficient (GPx-1(-/-)) mice during the aging process with special emphasis on dysregulation (uncoupling) of the endothelial NO synthase. GPx-1(-/-) mice on a C57 black 6 (C57BL/6) background at 2, 6, and 12 months of age were used. Vascular function was significantly impaired in 12-month-old GPx-1(-/-) -mice as compared with age-matched controls. Oxidant formation, detected by 3-nitrotyrosine staining and dihydroethidine-based fluorescence microtopography, was increased in the aged GPx-1(-/-) mice. Aging per se caused a substantial protein kinase C- and protein tyrosine kinase-dependent phosphorylation as well as S-glutathionylation of endothelial NO synthase associated with uncoupling, a phenomenon that was more pronounced in aged GPx-1(-/-) mice. GPx-1 ablation increased adhesion of leukocytes to cultured endothelial cells and CD68 and F4/80 staining in cardiac tissue. Aged GPx-1(-/-) mice displayed increased oxidant formation as compared with their wild-type littermates, triggering redox-signaling pathways associated with endothelial NO synthase dysfunction and uncoupling. Thus, our data demonstrate that aging leads to decreased NO bioavailability because of endothelial NO synthase dysfunction and uncoupling of the enzyme leading to endothelial dysfunction, vascular remodeling, and promotion of adhesion and infiltration of leukocytes into cardiovascular tissue, all of which was more prominent in aged GPx-1(-/-) mice.

KW - Aged

KW - Aging/metabolism

KW - Animals

KW - Cells, Cultured

KW - Endothelial Cells/cytology

KW - Endothelium, Vascular/metabolism

KW - Glutathione Peroxidase/deficiency

KW - Humans

KW - Leukocytes/cytology

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Nitric Oxide Synthase Type III/metabolism

KW - Oxidants/metabolism

KW - Oxidative Stress/physiology

KW - Phosphorylation/physiology

U2 - 10.1161/HYPERTENSIONAHA.113.01602

DO - 10.1161/HYPERTENSIONAHA.113.01602

M3 - SCORING: Journal article

C2 - 24296279

VL - 63

SP - 390

EP - 396

JO - HYPERTENSION

JF - HYPERTENSION

SN - 0194-911X

IS - 2

ER -