Role of myeloperoxidase-derived oxidants in the induction of vascular smooth muscle cell damage

Research output: Contribution to journalJournal articlepeer-review

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Role of myeloperoxidase-derived oxidants in the induction of vascular smooth muscle cell damage. / Flouda, Konstantina; Mercer, John; Davies, Michael Jonathan; Hawkins, Clare Louise.

In: Free Radical Biology & Medicine, Vol. 166, 2021, p. 165-177.

Research output: Contribution to journalJournal articlepeer-review

Harvard

Flouda, K, Mercer, J, Davies, MJ & Hawkins, CL 2021, 'Role of myeloperoxidase-derived oxidants in the induction of vascular smooth muscle cell damage', Free Radical Biology & Medicine, vol. 166, pp. 165-177. https://doi.org/10.1016/j.freeradbiomed.2021.02.021

APA

Flouda, K., Mercer, J., Davies, M. J., & Hawkins, C. L. (2021). Role of myeloperoxidase-derived oxidants in the induction of vascular smooth muscle cell damage. Free Radical Biology & Medicine, 166, 165-177. https://doi.org/10.1016/j.freeradbiomed.2021.02.021

Vancouver

Flouda K, Mercer J, Davies MJ, Hawkins CL. Role of myeloperoxidase-derived oxidants in the induction of vascular smooth muscle cell damage. Free Radical Biology & Medicine. 2021;166:165-177. https://doi.org/10.1016/j.freeradbiomed.2021.02.021

Author

Flouda, Konstantina ; Mercer, John ; Davies, Michael Jonathan ; Hawkins, Clare Louise. / Role of myeloperoxidase-derived oxidants in the induction of vascular smooth muscle cell damage. In: Free Radical Biology & Medicine. 2021 ; Vol. 166. pp. 165-177.

Bibtex

@article{a7b4721cf8c64cdf9afefc5f78eb9315,
title = "Role of myeloperoxidase-derived oxidants in the induction of vascular smooth muscle cell damage",
abstract = "Myeloperoxidase (MPO) is released by activated immune cells and forms the oxidants hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN) from the competing substrates chloride and thiocyanate. MPO and the overproduction of HOCl are strongly linked with vascular cell dysfunction and inflammation in atherosclerosis. HOCl is highly reactive and causes marked cell dysfunction and death, whereas data with HOSCN are conflicting, and highly dependent on the nature of the cell type. In this study we have examined the reactivity of HOCl and HOSCN with human coronary artery smooth muscle cells (HCASMC), given the key role of this cell type in maintaining vascular function. HOCl reacts rapidly with the cells, resulting in extensive cell death by both necrosis and apoptosis, and increased levels of intracellular calcium. In contrast, HOSCN reacts more slowly, with cell death occurring only after prolonged incubation, and in the absence of the accumulation of intracellular calcium. Exposure of HCASMC to HOCl also influences mitochondrial respiration, decreases glycolysis, lactate release, the production of ATP, cellular thiols and glutathione levels. These changes occurred to varying extents on exposure of the cells to HOSCN, where evidence was also obtained for the reversible modification of cellular thiols. HOCl also induced alterations in the mRNA expression of multiple inflammatory and phenotypic genes. Interestingly, the extent and nature of these changes was highly dependent on the specific cell donor used, with more marked effects observed in cells isolated from diseased compared to healthy vessels. Overall, these data provide new insight into pathways promoting vascular dysfunction during chronic inflammation, support the use of thiocyanate as a means to modulate MPO-induced cellular damage in atherosclerosis.",
author = "Konstantina Flouda and John Mercer and Davies, {Michael Jonathan} and Hawkins, {Clare Louise}",
year = "2021",
doi = "10.1016/j.freeradbiomed.2021.02.021",
language = "English",
volume = "166",
pages = "165--177",
journal = "Free Radical Biology & Medicine",
issn = "0891-5849",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Role of myeloperoxidase-derived oxidants in the induction of vascular smooth muscle cell damage

AU - Flouda, Konstantina

AU - Mercer, John

AU - Davies, Michael Jonathan

AU - Hawkins, Clare Louise

PY - 2021

Y1 - 2021

N2 - Myeloperoxidase (MPO) is released by activated immune cells and forms the oxidants hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN) from the competing substrates chloride and thiocyanate. MPO and the overproduction of HOCl are strongly linked with vascular cell dysfunction and inflammation in atherosclerosis. HOCl is highly reactive and causes marked cell dysfunction and death, whereas data with HOSCN are conflicting, and highly dependent on the nature of the cell type. In this study we have examined the reactivity of HOCl and HOSCN with human coronary artery smooth muscle cells (HCASMC), given the key role of this cell type in maintaining vascular function. HOCl reacts rapidly with the cells, resulting in extensive cell death by both necrosis and apoptosis, and increased levels of intracellular calcium. In contrast, HOSCN reacts more slowly, with cell death occurring only after prolonged incubation, and in the absence of the accumulation of intracellular calcium. Exposure of HCASMC to HOCl also influences mitochondrial respiration, decreases glycolysis, lactate release, the production of ATP, cellular thiols and glutathione levels. These changes occurred to varying extents on exposure of the cells to HOSCN, where evidence was also obtained for the reversible modification of cellular thiols. HOCl also induced alterations in the mRNA expression of multiple inflammatory and phenotypic genes. Interestingly, the extent and nature of these changes was highly dependent on the specific cell donor used, with more marked effects observed in cells isolated from diseased compared to healthy vessels. Overall, these data provide new insight into pathways promoting vascular dysfunction during chronic inflammation, support the use of thiocyanate as a means to modulate MPO-induced cellular damage in atherosclerosis.

AB - Myeloperoxidase (MPO) is released by activated immune cells and forms the oxidants hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN) from the competing substrates chloride and thiocyanate. MPO and the overproduction of HOCl are strongly linked with vascular cell dysfunction and inflammation in atherosclerosis. HOCl is highly reactive and causes marked cell dysfunction and death, whereas data with HOSCN are conflicting, and highly dependent on the nature of the cell type. In this study we have examined the reactivity of HOCl and HOSCN with human coronary artery smooth muscle cells (HCASMC), given the key role of this cell type in maintaining vascular function. HOCl reacts rapidly with the cells, resulting in extensive cell death by both necrosis and apoptosis, and increased levels of intracellular calcium. In contrast, HOSCN reacts more slowly, with cell death occurring only after prolonged incubation, and in the absence of the accumulation of intracellular calcium. Exposure of HCASMC to HOCl also influences mitochondrial respiration, decreases glycolysis, lactate release, the production of ATP, cellular thiols and glutathione levels. These changes occurred to varying extents on exposure of the cells to HOSCN, where evidence was also obtained for the reversible modification of cellular thiols. HOCl also induced alterations in the mRNA expression of multiple inflammatory and phenotypic genes. Interestingly, the extent and nature of these changes was highly dependent on the specific cell donor used, with more marked effects observed in cells isolated from diseased compared to healthy vessels. Overall, these data provide new insight into pathways promoting vascular dysfunction during chronic inflammation, support the use of thiocyanate as a means to modulate MPO-induced cellular damage in atherosclerosis.

U2 - 10.1016/j.freeradbiomed.2021.02.021

DO - 10.1016/j.freeradbiomed.2021.02.021

M3 - Journal article

C2 - 33631301

VL - 166

SP - 165

EP - 177

JO - Free Radical Biology & Medicine

JF - Free Radical Biology & Medicine

SN - 0891-5849

ER -

ID: 259157048