Deletion of vascular thromboxane A2 receptors and its impact on angiotensin II-induced hypertension and atherosclerotic lesion formation in the aorta of Ldlr-deficient mice

Heike Braun; Michael Hauke; Markus Petermann; Robert Eckenstaler; Anne Ripperger; Edzard Schwedhelm; Beatrice Ludwig-Kraus; Frank Bernhard Kraus; Md Jalal Ahmed Shawon; Virginie Dubourg; Alma Zernecke; Barbara Schreier; Michael Gekle; Ralf A Benndorf

doi:10.1016/j.bcp.2023.115916

Deletion of vascular thromboxane A2 receptors and its impact on angiotensin II-induced hypertension and atherosclerotic lesion formation in the aorta of Ldlr-deficient mice

Standard

Deletion of vascular thromboxane A2 receptors and its impact on angiotensin II-induced hypertension and atherosclerotic lesion formation in the aorta of Ldlr-deficient mice. / Braun, Heike; Hauke, Michael; Petermann, Markus; Eckenstaler, Robert; Ripperger, Anne; Schwedhelm, Edzard; Ludwig-Kraus, Beatrice; Bernhard Kraus, Frank; Jalal Ahmed Shawon, Md; Dubourg, Virginie; Zernecke, Alma; Schreier, Barbara; Gekle, Michael; Benndorf, Ralf A.

In: BIOCHEM PHARMACOL, Vol. 219, 115916, 01.2024.

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

Harvard

Braun, H, Hauke, M, Petermann, M, Eckenstaler, R, Ripperger, A, Schwedhelm, E, Ludwig-Kraus, B, Bernhard Kraus, F, Jalal Ahmed Shawon, M, Dubourg, V, Zernecke, A, Schreier, B, Gekle, M & Benndorf, RA 2024, 'Deletion of vascular thromboxane A2 receptors and its impact on angiotensin II-induced hypertension and atherosclerotic lesion formation in the aorta of Ldlr-deficient mice', BIOCHEM PHARMACOL, vol. 219, 115916. https://doi.org/10.1016/j.bcp.2023.115916

APA

Braun, H., Hauke, M., Petermann, M., Eckenstaler, R., Ripperger, A., Schwedhelm, E., Ludwig-Kraus, B., Bernhard Kraus, F., Jalal Ahmed Shawon, M., Dubourg, V., Zernecke, A., Schreier, B., Gekle, M., & Benndorf, R. A. (2024). Deletion of vascular thromboxane A2 receptors and its impact on angiotensin II-induced hypertension and atherosclerotic lesion formation in the aorta of Ldlr-deficient mice. BIOCHEM PHARMACOL, 219, [115916]. https://doi.org/10.1016/j.bcp.2023.115916

Vancouver

Braun H, Hauke M, Petermann M, Eckenstaler R, Ripperger A, Schwedhelm E et al. Deletion of vascular thromboxane A2 receptors and its impact on angiotensin II-induced hypertension and atherosclerotic lesion formation in the aorta of Ldlr-deficient mice. BIOCHEM PHARMACOL. 2024 Jan;219. 115916. https://doi.org/10.1016/j.bcp.2023.115916

Bibtex

@article{b6cab23e98834879ba7dd25a73a16ae1,

title = "Deletion of vascular thromboxane A2 receptors and its impact on angiotensin II-induced hypertension and atherosclerotic lesion formation in the aorta of Ldlr-deficient mice",

abstract = "The thromboxane A2 receptor (TP) has been shown to play a role in angiotensin II (Ang II)-mediated hypertension and pathological vascular remodeling. To assess the impact of vascular TP on Ang II-induced hypertension, atherogenesis, and pathological aortic alterations, i.e. aneurysms, we analysed Western-type diet-fed and Ang II-infused TPVSMC KO/Ldlr KO, TPEC KO/Ldlr KO mice and their respective wild-type littermates (TPWT/Ldlr KO). These analyses showed that neither EC- nor VSMC-specific deletion of the TP significantly affected basal or Ang II-induced blood pressure or aortic atherosclerotic lesion area. In contrast, VSMC-specific TP deletion abolished and EC-specific TP deletion surprisingly reduced the ex vivo reactivity of aortic rings to the TP agonist U-46619, whereas VSMC-specific TP knockout also diminished the ex vivo response of aortic rings to Ang II. Furthermore, despite similar systemic blood pressure, there was a trend towards less atherogenesis in the aortic arch and a trend towards fewer pathological aortic alterations in Ang II-treated female TPVSMC KO/Ldlr KO mice. Survival was impaired in male mice after Ang II infusion and tended to be higher in TPVSMC KO/Ldlr KO mice than in TPWT/Ldlr KO littermates. Thus, our data may suggest a deleterious role of the TP expressed in VSMC in the pathogenesis of Ang II-induced aortic atherosclerosis in female mice, and a surprising role of the endothelial TP in TP-mediated aortic contraction. However, future studies are needed to substantiate and further elucidate the role of the vascular TP in the pathogenesis of Ang II-induced hypertension, aortic atherosclerosis and aneurysm formation.",

keywords = "Animals, Female, Male, Mice, Angiotensin II/toxicity, Aorta, Atherosclerosis/chemically induced, Hypertension/chemically induced, Mice, Inbred C57BL, Mice, Knockout, Receptors, Thromboxane/genetics",

author = "Heike Braun and Michael Hauke and Markus Petermann and Robert Eckenstaler and Anne Ripperger and Edzard Schwedhelm and Beatrice Ludwig-Kraus and {Bernhard Kraus}, Frank and {Jalal Ahmed Shawon}, Md and Virginie Dubourg and Alma Zernecke and Barbara Schreier and Michael Gekle and Benndorf, {Ralf A}",

year = "2024",

month = jan,

doi = "10.1016/j.bcp.2023.115916",

language = "English",

volume = "219",

journal = "BIOCHEM PHARMACOL",

issn = "0006-2952",

publisher = "Elsevier Inc.",

}

RIS

TY - JOUR

T1 - Deletion of vascular thromboxane A2 receptors and its impact on angiotensin II-induced hypertension and atherosclerotic lesion formation in the aorta of Ldlr-deficient mice

AU - Braun, Heike

AU - Hauke, Michael

AU - Petermann, Markus

AU - Eckenstaler, Robert

AU - Ripperger, Anne

AU - Schwedhelm, Edzard

AU - Ludwig-Kraus, Beatrice

AU - Bernhard Kraus, Frank

AU - Jalal Ahmed Shawon, Md

AU - Dubourg, Virginie

AU - Zernecke, Alma

AU - Schreier, Barbara

AU - Gekle, Michael

AU - Benndorf, Ralf A

PY - 2024/1

Y1 - 2024/1

N2 - The thromboxane A2 receptor (TP) has been shown to play a role in angiotensin II (Ang II)-mediated hypertension and pathological vascular remodeling. To assess the impact of vascular TP on Ang II-induced hypertension, atherogenesis, and pathological aortic alterations, i.e. aneurysms, we analysed Western-type diet-fed and Ang II-infused TPVSMC KO/Ldlr KO, TPEC KO/Ldlr KO mice and their respective wild-type littermates (TPWT/Ldlr KO). These analyses showed that neither EC- nor VSMC-specific deletion of the TP significantly affected basal or Ang II-induced blood pressure or aortic atherosclerotic lesion area. In contrast, VSMC-specific TP deletion abolished and EC-specific TP deletion surprisingly reduced the ex vivo reactivity of aortic rings to the TP agonist U-46619, whereas VSMC-specific TP knockout also diminished the ex vivo response of aortic rings to Ang II. Furthermore, despite similar systemic blood pressure, there was a trend towards less atherogenesis in the aortic arch and a trend towards fewer pathological aortic alterations in Ang II-treated female TPVSMC KO/Ldlr KO mice. Survival was impaired in male mice after Ang II infusion and tended to be higher in TPVSMC KO/Ldlr KO mice than in TPWT/Ldlr KO littermates. Thus, our data may suggest a deleterious role of the TP expressed in VSMC in the pathogenesis of Ang II-induced aortic atherosclerosis in female mice, and a surprising role of the endothelial TP in TP-mediated aortic contraction. However, future studies are needed to substantiate and further elucidate the role of the vascular TP in the pathogenesis of Ang II-induced hypertension, aortic atherosclerosis and aneurysm formation.

AB - The thromboxane A2 receptor (TP) has been shown to play a role in angiotensin II (Ang II)-mediated hypertension and pathological vascular remodeling. To assess the impact of vascular TP on Ang II-induced hypertension, atherogenesis, and pathological aortic alterations, i.e. aneurysms, we analysed Western-type diet-fed and Ang II-infused TPVSMC KO/Ldlr KO, TPEC KO/Ldlr KO mice and their respective wild-type littermates (TPWT/Ldlr KO). These analyses showed that neither EC- nor VSMC-specific deletion of the TP significantly affected basal or Ang II-induced blood pressure or aortic atherosclerotic lesion area. In contrast, VSMC-specific TP deletion abolished and EC-specific TP deletion surprisingly reduced the ex vivo reactivity of aortic rings to the TP agonist U-46619, whereas VSMC-specific TP knockout also diminished the ex vivo response of aortic rings to Ang II. Furthermore, despite similar systemic blood pressure, there was a trend towards less atherogenesis in the aortic arch and a trend towards fewer pathological aortic alterations in Ang II-treated female TPVSMC KO/Ldlr KO mice. Survival was impaired in male mice after Ang II infusion and tended to be higher in TPVSMC KO/Ldlr KO mice than in TPWT/Ldlr KO littermates. Thus, our data may suggest a deleterious role of the TP expressed in VSMC in the pathogenesis of Ang II-induced aortic atherosclerosis in female mice, and a surprising role of the endothelial TP in TP-mediated aortic contraction. However, future studies are needed to substantiate and further elucidate the role of the vascular TP in the pathogenesis of Ang II-induced hypertension, aortic atherosclerosis and aneurysm formation.

KW - Animals

KW - Female

KW - Male

KW - Mice

KW - Angiotensin II/toxicity

KW - Aorta

KW - Atherosclerosis/chemically induced

KW - Hypertension/chemically induced

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Receptors, Thromboxane/genetics

U2 - 10.1016/j.bcp.2023.115916

DO - 10.1016/j.bcp.2023.115916

M3 - SCORING: Journal article

C2 - 37979705

VL - 219

JO - BIOCHEM PHARMACOL

JF - BIOCHEM PHARMACOL

SN - 0006-2952

M1 - 115916

ER -