MyD88 in myeloid cells drives angiotensin II-induced vascular inflammation, is associated with prevalent heart failure, and predicts all-cause mortality in arterial hypertension

Sabine Wild; Stefanie Finger; Andreas Schulz; Melania Aluia; Jimena Bravo; Rahul Kumar; Jeremy Lagrange; Gregorio Alanis-Lobato; Voahanginirina Randriamboavonjy; Johannes Wild; Michael Molitor; Christian Müller; Tanja Zeller; Alexander Gieswinkel; Andreas Daiber; Susanne Helena Karbach; Marcus Dörr; Ingrid Fleming; Philipp Lurz; Thomas Münzel; Markus Radsak; Katrin Schäfer; Daniela S Krause; Miguel A Andrade-Navarro; Philipp Wild; Philip Wenzel

doi:10.1093/ehjopen/oeag031

MyD88 in myeloid cells drives angiotensin II-induced vascular inflammation, is associated with prevalent heart failure, and predicts all-cause mortality in arterial hypertension

Sabine Wild, Stefanie Finger, Andreas Schulz, Melania Aluia, Jimena Bravo, Rahul Kumar, Jeremy Lagrange, Gregorio Alanis-Lobato, Voahanginirina Randriamboavonjy, Johannes Wild, Michael Molitor, Christian Müller, Tanja Zeller, Alexander Gieswinkel, Andreas Daiber, Susanne Helena Karbach, Marcus Dörr, Ingrid Fleming, Philipp Lurz, Thomas MünzelMarkus Radsak, Katrin Schäfer, Daniela S Krause, Miguel A Andrade-Navarro, Philipp Wild, Philip Wenzel

Abstract

AIMS: Angiotensin II (AngII) causes hypertension and vascular inflammation and is essential in neurohumoral activation promoting the development of heart failure. The role of the adaptor protein myeloid factor of differentiation 88 (MyD88) driving this pathology remains incompletely understood.

METHODS AND RESULTS: Male C57BL/6JMyD88-/-, LysMCre/wtMyD88LSL/LSL, LysMCre/wt, TLR2-/-, TLR4-/-, TLR7-/-, and TLR9-/- mice were investigated (1 mg/AngIIkg/d for 7 days). Additionally, we performed biodata analyses from a population-based cohort study and human protein network interactome analyses to understand the role of MyD88 in hypertension. MyD88 deficiency attenuated AngII-induced hypertension and endothelial dysfunction in conductance and resistance vessels, surpassing the effect of single TLR deficiencies. Vascular mRNA expression levels of vcam-1, nos2, nox2, cd62L, cd68, ccl2, il12, and il1b and accumulation of CD11b+Ly6Chi inflammatory monocytes and interferon-g+ NK cells were significantly dampened in MyD88-/-. Vascular protection was conferred by MyD88 deficiency in bone marrow-derived cells. Re-expression of MyD88 in LysMCre/wtMyD88LSL/LSL mice restored AngII-induced pathology, revealing that myeloid cells drive vascular dysfunction in a MyD88-dependent manner. Computational analyses of the human protein interactome demonstrated that MyD88 expression significantly associates with proteins encoded by genetic loci associated with blood pressure traits in multiple GWAS. In hypertensive individuals of the Gutenberg Health Study, monocytic MyD88 mRNA expression was associated with prevalent heart failure and all-cause mortality after a median follow-up of 16.5 years.

CONCLUSION: MyD88 promotes AngII-induced vascular dysfunction and arterial hypertension and might serve as both an inflammatory diagnostic marker and a drug target to tackle the risk of death and incident heart failure in hypertensive patients.

Original language	English
Journal	European Heart Journal Open
Volume	6
Issue number	2
Pages (from-to)	oeag031
DOIs	https://doi.org/10.1093/ehjopen/oeag031
Publication status	Published - 03.2026

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This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being
SDG 10 Reduced Inequalities

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10.1093/ehjopen/oeag031

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Wild, S., Finger, S., Schulz, A., Aluia, M., Bravo, J., Kumar, R., Lagrange, J., Alanis-Lobato, G., Randriamboavonjy, V., Wild, J., Molitor, M., Müller, C., Zeller, T., Gieswinkel, A., Daiber, A., Karbach, S. H., Dörr, M., Fleming, I., Lurz, P., ... Wenzel, P. (2026). MyD88 in myeloid cells drives angiotensin II-induced vascular inflammation, is associated with prevalent heart failure, and predicts all-cause mortality in arterial hypertension. European Heart Journal Open, 6(2), oeag031. https://doi.org/10.1093/ehjopen/oeag031

@article{50aeb993c4454eb1a5ef090660820962,

title = "MyD88 in myeloid cells drives angiotensin II-induced vascular inflammation, is associated with prevalent heart failure, and predicts all-cause mortality in arterial hypertension",

abstract = "AIMS: Angiotensin II (AngII) causes hypertension and vascular inflammation and is essential in neurohumoral activation promoting the development of heart failure. The role of the adaptor protein myeloid factor of differentiation 88 (MyD88) driving this pathology remains incompletely understood.METHODS AND RESULTS: Male C57BL/6JMyD88-/-, LysMCre/wtMyD88LSL/LSL, LysMCre/wt, TLR2-/-, TLR4-/-, TLR7-/-, and TLR9-/- mice were investigated (1 mg/AngIIkg/d for 7 days). Additionally, we performed biodata analyses from a population-based cohort study and human protein network interactome analyses to understand the role of MyD88 in hypertension. MyD88 deficiency attenuated AngII-induced hypertension and endothelial dysfunction in conductance and resistance vessels, surpassing the effect of single TLR deficiencies. Vascular mRNA expression levels of vcam-1, nos2, nox2, cd62L, cd68, ccl2, il12, and il1b and accumulation of CD11b+Ly6Chi inflammatory monocytes and interferon-g+ NK cells were significantly dampened in MyD88-/-. Vascular protection was conferred by MyD88 deficiency in bone marrow-derived cells. Re-expression of MyD88 in LysMCre/wtMyD88LSL/LSL mice restored AngII-induced pathology, revealing that myeloid cells drive vascular dysfunction in a MyD88-dependent manner. Computational analyses of the human protein interactome demonstrated that MyD88 expression significantly associates with proteins encoded by genetic loci associated with blood pressure traits in multiple GWAS. In hypertensive individuals of the Gutenberg Health Study, monocytic MyD88 mRNA expression was associated with prevalent heart failure and all-cause mortality after a median follow-up of 16.5 years.CONCLUSION: MyD88 promotes AngII-induced vascular dysfunction and arterial hypertension and might serve as both an inflammatory diagnostic marker and a drug target to tackle the risk of death and incident heart failure in hypertensive patients.",

author = "Sabine Wild and Stefanie Finger and Andreas Schulz and Melania Aluia and Jimena Bravo and Rahul Kumar and Jeremy Lagrange and Gregorio Alanis-Lobato and Voahanginirina Randriamboavonjy and Johannes Wild and Michael Molitor and Christian M{\"u}ller and Tanja Zeller and Alexander Gieswinkel and Andreas Daiber and Karbach, \{Susanne Helena\} and Marcus D{\"o}rr and Ingrid Fleming and Philipp Lurz and Thomas M{\"u}nzel and Markus Radsak and Katrin Sch{\"a}fer and Krause, \{Daniela S\} and Andrade-Navarro, \{Miguel A\} and Philipp Wild and Philip Wenzel",

note = "{\textcopyright} The Author(s) 2026. Published by Oxford University Press on behalf of the European Society of Cardiology.",

year = "2026",

month = mar,

doi = "10.1093/ehjopen/oeag031",

language = "English",

volume = "6",

pages = "oeag031",

journal = "European Heart Journal Open",

issn = "2752-4191",

publisher = "Oxford University Press",

number = "2",

}

Wild, S, Finger, S, Schulz, A, Aluia, M, Bravo, J, Kumar, R, Lagrange, J, Alanis-Lobato, G, Randriamboavonjy, V, Wild, J, Molitor, M, Müller, C, Zeller, T, Gieswinkel, A, Daiber, A, Karbach, SH, Dörr, M, Fleming, I, Lurz, P, Münzel, T, Radsak, M, Schäfer, K, Krause, DS, Andrade-Navarro, MA, Wild, P & Wenzel, P 2026, 'MyD88 in myeloid cells drives angiotensin II-induced vascular inflammation, is associated with prevalent heart failure, and predicts all-cause mortality in arterial hypertension', European Heart Journal Open, vol. 6, no. 2, pp. oeag031. https://doi.org/10.1093/ehjopen/oeag031

MyD88 in myeloid cells drives angiotensin II-induced vascular inflammation, is associated with prevalent heart failure, and predicts all-cause mortality in arterial hypertension. / Wild, Sabine; Finger, Stefanie; Schulz, Andreas et al.
In: European Heart Journal Open, Vol. 6, No. 2, 03.2026, p. oeag031.

Research output: Journal Articles › Journal articles › Research › peer-review

TY - JOUR

T1 - MyD88 in myeloid cells drives angiotensin II-induced vascular inflammation, is associated with prevalent heart failure, and predicts all-cause mortality in arterial hypertension

AU - Wild, Sabine

AU - Finger, Stefanie

AU - Schulz, Andreas

AU - Aluia, Melania

AU - Bravo, Jimena

AU - Kumar, Rahul

AU - Lagrange, Jeremy

AU - Alanis-Lobato, Gregorio

AU - Randriamboavonjy, Voahanginirina

AU - Wild, Johannes

AU - Molitor, Michael

AU - Müller, Christian

AU - Zeller, Tanja

AU - Gieswinkel, Alexander

AU - Daiber, Andreas

AU - Karbach, Susanne Helena

AU - Dörr, Marcus

AU - Fleming, Ingrid

AU - Lurz, Philipp

AU - Münzel, Thomas

AU - Radsak, Markus

AU - Schäfer, Katrin

AU - Krause, Daniela S

AU - Andrade-Navarro, Miguel A

AU - Wild, Philipp

AU - Wenzel, Philip

PY - 2026/3

Y1 - 2026/3

N2 - AIMS: Angiotensin II (AngII) causes hypertension and vascular inflammation and is essential in neurohumoral activation promoting the development of heart failure. The role of the adaptor protein myeloid factor of differentiation 88 (MyD88) driving this pathology remains incompletely understood.METHODS AND RESULTS: Male C57BL/6JMyD88-/-, LysMCre/wtMyD88LSL/LSL, LysMCre/wt, TLR2-/-, TLR4-/-, TLR7-/-, and TLR9-/- mice were investigated (1 mg/AngIIkg/d for 7 days). Additionally, we performed biodata analyses from a population-based cohort study and human protein network interactome analyses to understand the role of MyD88 in hypertension. MyD88 deficiency attenuated AngII-induced hypertension and endothelial dysfunction in conductance and resistance vessels, surpassing the effect of single TLR deficiencies. Vascular mRNA expression levels of vcam-1, nos2, nox2, cd62L, cd68, ccl2, il12, and il1b and accumulation of CD11b+Ly6Chi inflammatory monocytes and interferon-g+ NK cells were significantly dampened in MyD88-/-. Vascular protection was conferred by MyD88 deficiency in bone marrow-derived cells. Re-expression of MyD88 in LysMCre/wtMyD88LSL/LSL mice restored AngII-induced pathology, revealing that myeloid cells drive vascular dysfunction in a MyD88-dependent manner. Computational analyses of the human protein interactome demonstrated that MyD88 expression significantly associates with proteins encoded by genetic loci associated with blood pressure traits in multiple GWAS. In hypertensive individuals of the Gutenberg Health Study, monocytic MyD88 mRNA expression was associated with prevalent heart failure and all-cause mortality after a median follow-up of 16.5 years.CONCLUSION: MyD88 promotes AngII-induced vascular dysfunction and arterial hypertension and might serve as both an inflammatory diagnostic marker and a drug target to tackle the risk of death and incident heart failure in hypertensive patients.

AB - AIMS: Angiotensin II (AngII) causes hypertension and vascular inflammation and is essential in neurohumoral activation promoting the development of heart failure. The role of the adaptor protein myeloid factor of differentiation 88 (MyD88) driving this pathology remains incompletely understood.METHODS AND RESULTS: Male C57BL/6JMyD88-/-, LysMCre/wtMyD88LSL/LSL, LysMCre/wt, TLR2-/-, TLR4-/-, TLR7-/-, and TLR9-/- mice were investigated (1 mg/AngIIkg/d for 7 days). Additionally, we performed biodata analyses from a population-based cohort study and human protein network interactome analyses to understand the role of MyD88 in hypertension. MyD88 deficiency attenuated AngII-induced hypertension and endothelial dysfunction in conductance and resistance vessels, surpassing the effect of single TLR deficiencies. Vascular mRNA expression levels of vcam-1, nos2, nox2, cd62L, cd68, ccl2, il12, and il1b and accumulation of CD11b+Ly6Chi inflammatory monocytes and interferon-g+ NK cells were significantly dampened in MyD88-/-. Vascular protection was conferred by MyD88 deficiency in bone marrow-derived cells. Re-expression of MyD88 in LysMCre/wtMyD88LSL/LSL mice restored AngII-induced pathology, revealing that myeloid cells drive vascular dysfunction in a MyD88-dependent manner. Computational analyses of the human protein interactome demonstrated that MyD88 expression significantly associates with proteins encoded by genetic loci associated with blood pressure traits in multiple GWAS. In hypertensive individuals of the Gutenberg Health Study, monocytic MyD88 mRNA expression was associated with prevalent heart failure and all-cause mortality after a median follow-up of 16.5 years.CONCLUSION: MyD88 promotes AngII-induced vascular dysfunction and arterial hypertension and might serve as both an inflammatory diagnostic marker and a drug target to tackle the risk of death and incident heart failure in hypertensive patients.

U2 - 10.1093/ehjopen/oeag031

DO - 10.1093/ehjopen/oeag031

M3 - Journal articles

C2 - 41993090

SN - 2752-4191

VL - 6

SP - oeag031

JO - European Heart Journal Open

JF - European Heart Journal Open

IS - 2

ER -

MyD88 in myeloid cells drives angiotensin II-induced vascular inflammation, is associated with prevalent heart failure, and predicts all-cause mortality in arterial hypertension

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