Recruited macrophages elicit atrial fibrillation

Maarten Hulsmans; Maximilian J. Schloss; I. Hsiu Lee; Aneesh Bapat; Yoshiko Iwamoto; Claudio Vinegoni; Alexandre Paccalet; Masahiro Yamazoe; Jana Grune; Steffen Pabel; Noor Momin; Hana Seung; Nina Kumowski; Fadi E. Pulous; Daniel Keller; Constanze Bening; Ursula Green; Jochen K. Lennerz; Richard N. Mitchell; Andrew Lewis; Barbara Casadei; Oriol Iborra-Egea; Antoni Bayes-Genis; Samuel Sossalla; Chin Siang Ong; Richard N. Pierson; Jon C. Aster; David Rohde; Gregory R. Wojtkiewicz; Ralph Weissleder; Filip K. Swirski; George Tellides; George Tolis; Serguei Melnitchouk; David J. Milan; Patrick T. Ellinor; Kamila Naxerova; Matthias Nahrendorf

doi:10.1126/science.abq3061

Recruited macrophages elicit atrial fibrillation

Maarten Hulsmans, Maximilian J. Schloss, I. Hsiu Lee, Aneesh Bapat, Yoshiko Iwamoto, Claudio Vinegoni, Alexandre Paccalet, Masahiro Yamazoe, Jana Grune, Steffen Pabel, Noor Momin, Hana Seung, Nina Kumowski, Fadi E. Pulous, Daniel Keller, Constanze Bening, Ursula Green, Jochen K. Lennerz, Richard N. Mitchell, Andrew LewisBarbara Casadei, Oriol Iborra-Egea, Antoni Bayes-Genis, Samuel Sossalla, Chin Siang Ong, Richard N. Pierson, Jon C. Aster, David Rohde, Gregory R. Wojtkiewicz, Ralph Weissleder, Filip K. Swirski, George Tellides, George Tolis, Serguei Melnitchouk, David J. Milan, Patrick T. Ellinor, Kamila Naxerova, Matthias Nahrendorf

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88 Scopus citations

Abstract

Atrial fibrillation disrupts contraction of the atria, leading to stroke and heart failure. We deciphered how immune and stromal cells contribute to atrial fibrillation. Single-cell transcriptomes from human atria documented inflammatory monocyte and SPP1+ macrophage expansion in atrial fibrillation. Combining hypertension, obesity, and mitral valve regurgitation (HOMER) in mice elicited enlarged, fibrosed, and fibrillation-prone atria. Single-cell transcriptomes from HOMER mouse atria recapitulated cell composition and transcriptome changes observed in patients. Inhibiting monocyte migration reduced arrhythmia in Ccr2-/- HOMER mice. Cell-cell interaction analysis identified SPP1 as a pleiotropic signal that promotes atrial fibrillation through cross-talk with local immune and stromal cells. Deleting Spp1 reduced atrial fibrillation in HOMER mice. These results identify SPP1+ macrophages as targets for immunotherapy in atrial fibrillation.

Original language	English
Pages (from-to)	231-239
Number of pages	9
Journal	Science
Volume	381
Issue number	6654
DOIs	https://doi.org/10.1126/science.abq3061
State	Published - 14 Jul 2023

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Hulsmans, M., Schloss, M. J., Lee, I. H., Bapat, A., Iwamoto, Y., Vinegoni, C., Paccalet, A., Yamazoe, M., Grune, J., Pabel, S., Momin, N., Seung, H., Kumowski, N., Pulous, F. E., Keller, D., Bening, C., Green, U., Lennerz, J. K., Mitchell, R. N., ... Nahrendorf, M. (2023). Recruited macrophages elicit atrial fibrillation. Science, 381(6654), 231-239. https://doi.org/10.1126/science.abq3061

@article{ffc9c1db085f4060923b3a26b9d364ab,

title = "Recruited macrophages elicit atrial fibrillation",

abstract = "Atrial fibrillation disrupts contraction of the atria, leading to stroke and heart failure. We deciphered how immune and stromal cells contribute to atrial fibrillation. Single-cell transcriptomes from human atria documented inflammatory monocyte and SPP1+ macrophage expansion in atrial fibrillation. Combining hypertension, obesity, and mitral valve regurgitation (HOMER) in mice elicited enlarged, fibrosed, and fibrillation-prone atria. Single-cell transcriptomes from HOMER mouse atria recapitulated cell composition and transcriptome changes observed in patients. Inhibiting monocyte migration reduced arrhythmia in Ccr2-/- HOMER mice. Cell-cell interaction analysis identified SPP1 as a pleiotropic signal that promotes atrial fibrillation through cross-talk with local immune and stromal cells. Deleting Spp1 reduced atrial fibrillation in HOMER mice. These results identify SPP1+ macrophages as targets for immunotherapy in atrial fibrillation.",

author = "Maarten Hulsmans and Schloss, {Maximilian J.} and Lee, {I. Hsiu} and Aneesh Bapat and Yoshiko Iwamoto and Claudio Vinegoni and Alexandre Paccalet and Masahiro Yamazoe and Jana Grune and Steffen Pabel and Noor Momin and Hana Seung and Nina Kumowski and Pulous, {Fadi E.} and Daniel Keller and Constanze Bening and Ursula Green and Lennerz, {Jochen K.} and Mitchell, {Richard N.} and Andrew Lewis and Barbara Casadei and Oriol Iborra-Egea and Antoni Bayes-Genis and Samuel Sossalla and Ong, {Chin Siang} and Pierson, {Richard N.} and Aster, {Jon C.} and David Rohde and Wojtkiewicz, {Gregory R.} and Ralph Weissleder and Swirski, {Filip K.} and George Tellides and George Tolis and Serguei Melnitchouk and Milan, {David J.} and Ellinor, {Patrick T.} and Kamila Naxerova and Matthias Nahrendorf",

year = "2023",

month = jul,

day = "14",

doi = "10.1126/science.abq3061",

language = "English",

volume = "381",

pages = "231--239",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

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Hulsmans, M, Schloss, MJ, Lee, IH, Bapat, A, Iwamoto, Y, Vinegoni, C, Paccalet, A, Yamazoe, M, Grune, J, Pabel, S, Momin, N, Seung, H, Kumowski, N, Pulous, FE, Keller, D, Bening, C, Green, U, Lennerz, JK, Mitchell, RN, Lewis, A, Casadei, B, Iborra-Egea, O, Bayes-Genis, A, Sossalla, S, Ong, CS, Pierson, RN, Aster, JC, Rohde, D, Wojtkiewicz, GR, Weissleder, R, Swirski, FK, Tellides, G, Tolis, G, Melnitchouk, S, Milan, DJ, Ellinor, PT, Naxerova, K & Nahrendorf, M 2023, 'Recruited macrophages elicit atrial fibrillation', Science, vol. 381, no. 6654, pp. 231-239. https://doi.org/10.1126/science.abq3061

TY - JOUR

T1 - Recruited macrophages elicit atrial fibrillation

AU - Hulsmans, Maarten

AU - Schloss, Maximilian J.

AU - Lee, I. Hsiu

AU - Bapat, Aneesh

AU - Iwamoto, Yoshiko

AU - Vinegoni, Claudio

AU - Paccalet, Alexandre

AU - Yamazoe, Masahiro

AU - Grune, Jana

AU - Pabel, Steffen

AU - Momin, Noor

AU - Seung, Hana

AU - Kumowski, Nina

AU - Pulous, Fadi E.

AU - Keller, Daniel

AU - Bening, Constanze

AU - Green, Ursula

AU - Lennerz, Jochen K.

AU - Mitchell, Richard N.

AU - Lewis, Andrew

AU - Casadei, Barbara

AU - Iborra-Egea, Oriol

AU - Bayes-Genis, Antoni

AU - Sossalla, Samuel

AU - Ong, Chin Siang

AU - Pierson, Richard N.

AU - Aster, Jon C.

AU - Rohde, David

AU - Wojtkiewicz, Gregory R.

AU - Weissleder, Ralph

AU - Swirski, Filip K.

AU - Tellides, George

AU - Tolis, George

AU - Melnitchouk, Serguei

AU - Milan, David J.

AU - Ellinor, Patrick T.

AU - Naxerova, Kamila

AU - Nahrendorf, Matthias

PY - 2023/7/14

Y1 - 2023/7/14

N2 - Atrial fibrillation disrupts contraction of the atria, leading to stroke and heart failure. We deciphered how immune and stromal cells contribute to atrial fibrillation. Single-cell transcriptomes from human atria documented inflammatory monocyte and SPP1+ macrophage expansion in atrial fibrillation. Combining hypertension, obesity, and mitral valve regurgitation (HOMER) in mice elicited enlarged, fibrosed, and fibrillation-prone atria. Single-cell transcriptomes from HOMER mouse atria recapitulated cell composition and transcriptome changes observed in patients. Inhibiting monocyte migration reduced arrhythmia in Ccr2-/- HOMER mice. Cell-cell interaction analysis identified SPP1 as a pleiotropic signal that promotes atrial fibrillation through cross-talk with local immune and stromal cells. Deleting Spp1 reduced atrial fibrillation in HOMER mice. These results identify SPP1+ macrophages as targets for immunotherapy in atrial fibrillation.

AB - Atrial fibrillation disrupts contraction of the atria, leading to stroke and heart failure. We deciphered how immune and stromal cells contribute to atrial fibrillation. Single-cell transcriptomes from human atria documented inflammatory monocyte and SPP1+ macrophage expansion in atrial fibrillation. Combining hypertension, obesity, and mitral valve regurgitation (HOMER) in mice elicited enlarged, fibrosed, and fibrillation-prone atria. Single-cell transcriptomes from HOMER mouse atria recapitulated cell composition and transcriptome changes observed in patients. Inhibiting monocyte migration reduced arrhythmia in Ccr2-/- HOMER mice. Cell-cell interaction analysis identified SPP1 as a pleiotropic signal that promotes atrial fibrillation through cross-talk with local immune and stromal cells. Deleting Spp1 reduced atrial fibrillation in HOMER mice. These results identify SPP1+ macrophages as targets for immunotherapy in atrial fibrillation.

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U2 - 10.1126/science.abq3061

DO - 10.1126/science.abq3061

M3 - Article

C2 - 37440641

AN - SCOPUS:85164845934

SN - 0036-8075

VL - 381

SP - 231

EP - 239

JO - Science

JF - Science

IS - 6654

ER -

Recruited macrophages elicit atrial fibrillation

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