Research ExplorerPublicationsThe F2-isoprostane 8-iso-PGF2α attenuates atherosclerotic le...

The F2-isoprostane 8-iso-PGF2α attenuates atherosclerotic lesion formation in Ldlr-deficient mice - Potential role of vascular thromboxane A2 receptors

Standard

The F2-isoprostane 8-iso-PGF2α attenuates atherosclerotic lesion formation in Ldlr-deficient mice - Potential role of vascular thromboxane A2 receptors. / Braun, Heike; Hauke, Michael; Eckenstaler, Robert; Petermann, Markus; Ripperger, Anne; Kühn, Niklas; Schwedhelm, Edzard; Ludwig-Kraus, Beatrice; Kraus, Frank Bernhard; Dubourg, Virginie; Zernecke, Alma; Schreier, Barbara; Gekle, Michael; Benndorf, Ralf A.

In: FREE RADICAL BIO MED, Vol. 185, 20.05.2022, p. 36-45.

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

Harvard

Braun, H, Hauke, M, Eckenstaler, R, Petermann, M, Ripperger, A, Kühn, N, Schwedhelm, E, Ludwig-Kraus, B, Kraus, FB, Dubourg, V, Zernecke, A, Schreier, B, Gekle, M & Benndorf, RA 2022, 'The F2-isoprostane 8-iso-PGF2α attenuates atherosclerotic lesion formation in Ldlr-deficient mice - Potential role of vascular thromboxane A2 receptors', FREE RADICAL BIO MED, vol. 185, pp. 36-45. https://doi.org/10.1016/j.freeradbiomed.2022.04.010

APA

Braun, H., Hauke, M., Eckenstaler, R., Petermann, M., Ripperger, A., Kühn, N., Schwedhelm, E., Ludwig-Kraus, B., Kraus, F. B., Dubourg, V., Zernecke, A., Schreier, B., Gekle, M., & Benndorf, R. A. (2022). The F2-isoprostane 8-iso-PGF2α attenuates atherosclerotic lesion formation in Ldlr-deficient mice - Potential role of vascular thromboxane A2 receptors. FREE RADICAL BIO MED, 185, 36-45. https://doi.org/10.1016/j.freeradbiomed.2022.04.010

Vancouver

Braun H, Hauke M, Eckenstaler R, Petermann M, Ripperger A, Kühn N et al. The F2-isoprostane 8-iso-PGF2α attenuates atherosclerotic lesion formation in Ldlr-deficient mice - Potential role of vascular thromboxane A2 receptors. FREE RADICAL BIO MED. 2022 May 20;185:36-45. https://doi.org/10.1016/j.freeradbiomed.2022.04.010

Bibtex

@article{9622fd07bc7d42ef986ace9ddc382c86,
title = "The F2-isoprostane 8-iso-PGF2α attenuates atherosclerotic lesion formation in Ldlr-deficient mice - Potential role of vascular thromboxane A2 receptors",
abstract = "The F2-isoprostane 8-iso-PGF2α (also known as 15-F2t-isoprostane, iPF2α-III, 8-epi PGF2α, 15(S)-8-iso-PGF2α, or 8-Isoprostane), a thromboxane A2 receptor (TP) agonist, stable biomarker of oxidative stress, and risk marker of cardiovascular disease, has been proposed to aggravate atherogenesis in genetic mouse models of atherosclerotic vascular disease. Moreover, the TP plays an eminent role in the pathophysiology of endothelial dysfunction, atherogenesis, and cardiovascular disease. Yet it is unknown, how the TP expressed by vascular cells affects atherogenesis or 8-iso-PGF2α-related effects in mouse models of atherosclerosis. We studied Ldlr-deficient vascular endothelial-specific (EC) and vascular smooth muscle cell (VSMC)-specific TP knockout mice (TPECKO/Ldlr KO; TPVSMCKO/Ldlr KO) and corresponding wild-type littermates (TPWT/Ldlr KO). The mice were fed a Western-type diet for eight weeks and received either 8-iso-PGF2α or vehicle infusions via osmotic pumps. Subsequently, arterial blood pressure, atherosclerotic lesion formation, and lipid profiles were analyzed. We found that VSMC-, but not EC-specific TP deletion, attenuated atherogenesis without affecting blood pressure or plasma lipid profiles of the mice. In contrast to a previous report, 8-iso-PGF2α tended to reduce atherogenesis in TPWT/Ldlr KO and TPEC KO/Ldlr KO mice, again without significantly affecting blood pressure or lipid profiles of these mice. However, no further reduction in atherogenesis was observed in 8-iso-PGF2α-treated TPVSMC KO/Ldlr KO mice. Our work suggests that the TP expressed in VSMC but not the TP expressed in EC is involved in atherosclerotic lesion formation in Ldlr-deficient mice. Furthermore, we report an inhibitory effect of 8-iso-PGF2α on atherogenesis in this experimental atherosclerosis model, which paradoxically appears to be related to the presence of the TP in VSMC.",
keywords = "Animals, Atherosclerosis/genetics, Cardiovascular Diseases, Dinoprost/analogs & derivatives, F2-Isoprostanes, Mice, Mice, Knockout, Placenta Growth Factor, Receptors, Thromboxane/genetics, Thromboxane A2, Thromboxanes",
author = "Heike Braun and Michael Hauke and Robert Eckenstaler and Markus Petermann and Anne Ripperger and Niklas K{\"u}hn and Edzard Schwedhelm and Beatrice Ludwig-Kraus and Kraus, {Frank Bernhard} and Virginie Dubourg and Alma Zernecke and Barbara Schreier and Michael Gekle and Benndorf, {Ralf A}",
note = "Copyright {\textcopyright} 2022 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2022",
month = may,
day = "20",
doi = "10.1016/j.freeradbiomed.2022.04.010",
language = "English",
volume = "185",
pages = "36--45",
journal = "FREE RADICAL BIO MED",
issn = "0891-5849",
publisher = "Elsevier Inc.",

}

RIS

TY - JOUR

T1 - The F2-isoprostane 8-iso-PGF2α attenuates atherosclerotic lesion formation in Ldlr-deficient mice - Potential role of vascular thromboxane A2 receptors

AU - Braun, Heike

AU - Hauke, Michael

AU - Eckenstaler, Robert

AU - Petermann, Markus

AU - Ripperger, Anne

AU - Kühn, Niklas

AU - Schwedhelm, Edzard

AU - Ludwig-Kraus, Beatrice

AU - Kraus, Frank Bernhard

AU - Dubourg, Virginie

AU - Zernecke, Alma

AU - Schreier, Barbara

AU - Gekle, Michael

AU - Benndorf, Ralf A

N1 - Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2022/5/20

Y1 - 2022/5/20

N2 - The F2-isoprostane 8-iso-PGF2α (also known as 15-F2t-isoprostane, iPF2α-III, 8-epi PGF2α, 15(S)-8-iso-PGF2α, or 8-Isoprostane), a thromboxane A2 receptor (TP) agonist, stable biomarker of oxidative stress, and risk marker of cardiovascular disease, has been proposed to aggravate atherogenesis in genetic mouse models of atherosclerotic vascular disease. Moreover, the TP plays an eminent role in the pathophysiology of endothelial dysfunction, atherogenesis, and cardiovascular disease. Yet it is unknown, how the TP expressed by vascular cells affects atherogenesis or 8-iso-PGF2α-related effects in mouse models of atherosclerosis. We studied Ldlr-deficient vascular endothelial-specific (EC) and vascular smooth muscle cell (VSMC)-specific TP knockout mice (TPECKO/Ldlr KO; TPVSMCKO/Ldlr KO) and corresponding wild-type littermates (TPWT/Ldlr KO). The mice were fed a Western-type diet for eight weeks and received either 8-iso-PGF2α or vehicle infusions via osmotic pumps. Subsequently, arterial blood pressure, atherosclerotic lesion formation, and lipid profiles were analyzed. We found that VSMC-, but not EC-specific TP deletion, attenuated atherogenesis without affecting blood pressure or plasma lipid profiles of the mice. In contrast to a previous report, 8-iso-PGF2α tended to reduce atherogenesis in TPWT/Ldlr KO and TPEC KO/Ldlr KO mice, again without significantly affecting blood pressure or lipid profiles of these mice. However, no further reduction in atherogenesis was observed in 8-iso-PGF2α-treated TPVSMC KO/Ldlr KO mice. Our work suggests that the TP expressed in VSMC but not the TP expressed in EC is involved in atherosclerotic lesion formation in Ldlr-deficient mice. Furthermore, we report an inhibitory effect of 8-iso-PGF2α on atherogenesis in this experimental atherosclerosis model, which paradoxically appears to be related to the presence of the TP in VSMC.

AB - The F2-isoprostane 8-iso-PGF2α (also known as 15-F2t-isoprostane, iPF2α-III, 8-epi PGF2α, 15(S)-8-iso-PGF2α, or 8-Isoprostane), a thromboxane A2 receptor (TP) agonist, stable biomarker of oxidative stress, and risk marker of cardiovascular disease, has been proposed to aggravate atherogenesis in genetic mouse models of atherosclerotic vascular disease. Moreover, the TP plays an eminent role in the pathophysiology of endothelial dysfunction, atherogenesis, and cardiovascular disease. Yet it is unknown, how the TP expressed by vascular cells affects atherogenesis or 8-iso-PGF2α-related effects in mouse models of atherosclerosis. We studied Ldlr-deficient vascular endothelial-specific (EC) and vascular smooth muscle cell (VSMC)-specific TP knockout mice (TPECKO/Ldlr KO; TPVSMCKO/Ldlr KO) and corresponding wild-type littermates (TPWT/Ldlr KO). The mice were fed a Western-type diet for eight weeks and received either 8-iso-PGF2α or vehicle infusions via osmotic pumps. Subsequently, arterial blood pressure, atherosclerotic lesion formation, and lipid profiles were analyzed. We found that VSMC-, but not EC-specific TP deletion, attenuated atherogenesis without affecting blood pressure or plasma lipid profiles of the mice. In contrast to a previous report, 8-iso-PGF2α tended to reduce atherogenesis in TPWT/Ldlr KO and TPEC KO/Ldlr KO mice, again without significantly affecting blood pressure or lipid profiles of these mice. However, no further reduction in atherogenesis was observed in 8-iso-PGF2α-treated TPVSMC KO/Ldlr KO mice. Our work suggests that the TP expressed in VSMC but not the TP expressed in EC is involved in atherosclerotic lesion formation in Ldlr-deficient mice. Furthermore, we report an inhibitory effect of 8-iso-PGF2α on atherogenesis in this experimental atherosclerosis model, which paradoxically appears to be related to the presence of the TP in VSMC.

KW - Animals

KW - Atherosclerosis/genetics

KW - Cardiovascular Diseases

KW - Dinoprost/analogs & derivatives

KW - F2-Isoprostanes

KW - Mice

KW - Mice, Knockout

KW - Placenta Growth Factor

KW - Receptors, Thromboxane/genetics

KW - Thromboxane A2

KW - Thromboxanes

U2 - 10.1016/j.freeradbiomed.2022.04.010

DO - 10.1016/j.freeradbiomed.2022.04.010

M3 - SCORING: Journal article

C2 - 35470061

VL - 185

SP - 36

EP - 45

JO - FREE RADICAL BIO MED

JF - FREE RADICAL BIO MED

SN - 0891-5849

ER -