TREM2 protects from atherosclerosis by limiting necrotic core formation

Marie Piollet; Florentina Porsch; Giuseppe Rizzo; Frederieke Kapser; Dirk J.J. Schulz; Máté G. Kiss; Kai Schlepckow; Estrella Morenas-Rodriguez; Mustafa Orkun Sen; Julius Gropper; Sourish Reddy Bandi; Sarah Schäfer; Tobias Krammer; Alexander M. Leipold; Matthias Hoke; Mária Ozsvár-Kozma; Hannah Beneš; Martin Schillinger; Erich Minar; Melanie Roesch; Laura Göderle; Anastasiya Hladik; Sylvia Knapp; Marco Colonna; Rudolf Martini; Antoine Emmanuel Saliba; Christian Haass; Alma Zernecke; Christoph J. Binder; Clément Cochain

doi:10.1038/s44161-024-00429-9

TREM2 protects from atherosclerosis by limiting necrotic core formation

Marie Piollet, Florentina Porsch, Giuseppe Rizzo, Frederieke Kapser, Dirk J.J. Schulz, Máté G. Kiss, Kai Schlepckow, Estrella Morenas-Rodriguez, Mustafa Orkun Sen, Julius Gropper, Sourish Reddy Bandi, Sarah Schäfer, Tobias Krammer, Alexander M. Leipold, Matthias Hoke, Mária Ozsvár-Kozma, Hannah Beneš, Martin Schillinger, Erich Minar, Melanie RoeschLaura Göderle, Anastasiya Hladik, Sylvia Knapp, Marco Colonna, Rudolf Martini, Antoine Emmanuel Saliba, Christian Haass, Alma Zernecke, Christoph J. Binder, Clément Cochain

Research output: Contribution to journal › Letter › peer-review

12 Scopus citations

Abstract

Atherosclerosis is a chronic disease of the vascular wall driven by lipid accumulation and inflammation in the intimal layer of arteries, and its main complications—myocardial infarction and stroke—are the leading cause of mortality worldwide^1,2. Recent studies have identified triggering receptor expressed on myeloid cells 2 (TREM2), a lipid-sensing receptor regulating myeloid cell functions³, to be highly expressed in macrophage foam cells in experimental and human atherosclerosis⁴. However, the role of TREM2 in atherosclerosis is not fully known. Here we show that hematopoietic or global TREM2 deficiency increased, whereas TREM2 agonism decreased, necrotic core formation in early atherosclerosis. We demonstrate that TREM2 is essential for the efferocytosis capacities of macrophages and to the survival of lipid-laden macrophages, indicating a crucial role of TREM2 in maintaining the balance between foam cell death and clearance of dead cells in atherosclerotic lesions, thereby controlling plaque necrosis.

Original language	English
Pages (from-to)	269-282
Number of pages	14
Journal	Nature Cardiovascular Research
Volume	3
Issue number	3
DOIs	https://doi.org/10.1038/s44161-024-00429-9
State	Published - Mar 2024

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Piollet, M., Porsch, F., Rizzo, G., Kapser, F., Schulz, D. J. J., Kiss, M. G., Schlepckow, K., Morenas-Rodriguez, E., Sen, M. O., Gropper, J., Bandi, S. R., Schäfer, S., Krammer, T., Leipold, A. M., Hoke, M., Ozsvár-Kozma, M., Beneš, H., Schillinger, M., Minar, E., ... Cochain, C. (2024). TREM2 protects from atherosclerosis by limiting necrotic core formation. Nature Cardiovascular Research, 3(3), 269-282. https://doi.org/10.1038/s44161-024-00429-9

@article{00242cd584b84c668966a2b0ca1013b6,

title = "TREM2 protects from atherosclerosis by limiting necrotic core formation",

abstract = "Atherosclerosis is a chronic disease of the vascular wall driven by lipid accumulation and inflammation in the intimal layer of arteries, and its main complications—myocardial infarction and stroke—are the leading cause of mortality worldwide1,2. Recent studies have identified triggering receptor expressed on myeloid cells 2 (TREM2), a lipid-sensing receptor regulating myeloid cell functions3, to be highly expressed in macrophage foam cells in experimental and human atherosclerosis4. However, the role of TREM2 in atherosclerosis is not fully known. Here we show that hematopoietic or global TREM2 deficiency increased, whereas TREM2 agonism decreased, necrotic core formation in early atherosclerosis. We demonstrate that TREM2 is essential for the efferocytosis capacities of macrophages and to the survival of lipid-laden macrophages, indicating a crucial role of TREM2 in maintaining the balance between foam cell death and clearance of dead cells in atherosclerotic lesions, thereby controlling plaque necrosis.",

author = "Marie Piollet and Florentina Porsch and Giuseppe Rizzo and Frederieke Kapser and Schulz, {Dirk J.J.} and Kiss, {M{\'a}t{\'e} G.} and Kai Schlepckow and Estrella Morenas-Rodriguez and Sen, {Mustafa Orkun} and Julius Gropper and Bandi, {Sourish Reddy} and Sarah Sch{\"a}fer and Tobias Krammer and Leipold, {Alexander M.} and Matthias Hoke and M{\'a}ria Ozsv{\'a}r-Kozma and Hannah Bene{\v s} and Martin Schillinger and Erich Minar and Melanie Roesch and Laura G{\"o}derle and Anastasiya Hladik and Sylvia Knapp and Marco Colonna and Rudolf Martini and Saliba, {Antoine Emmanuel} and Christian Haass and Alma Zernecke and Binder, {Christoph J.} and Cl{\'e}ment Cochain",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2024.",

year = "2024",

month = mar,

doi = "10.1038/s44161-024-00429-9",

language = "English",

volume = "3",

pages = "269--282",

journal = "Nature Cardiovascular Research",

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Piollet, M, Porsch, F, Rizzo, G, Kapser, F, Schulz, DJJ, Kiss, MG, Schlepckow, K, Morenas-Rodriguez, E, Sen, MO, Gropper, J, Bandi, SR, Schäfer, S, Krammer, T, Leipold, AM, Hoke, M, Ozsvár-Kozma, M, Beneš, H, Schillinger, M, Minar, E, Roesch, M, Göderle, L, Hladik, A, Knapp, S, Colonna, M, Martini, R, Saliba, AE, Haass, C, Zernecke, A, Binder, CJ & Cochain, C 2024, 'TREM2 protects from atherosclerosis by limiting necrotic core formation', Nature Cardiovascular Research, vol. 3, no. 3, pp. 269-282. https://doi.org/10.1038/s44161-024-00429-9

TY - JOUR

T1 - TREM2 protects from atherosclerosis by limiting necrotic core formation

AU - Piollet, Marie

AU - Porsch, Florentina

AU - Rizzo, Giuseppe

AU - Kapser, Frederieke

AU - Schulz, Dirk J.J.

AU - Kiss, Máté G.

AU - Schlepckow, Kai

AU - Morenas-Rodriguez, Estrella

AU - Sen, Mustafa Orkun

AU - Gropper, Julius

AU - Bandi, Sourish Reddy

AU - Schäfer, Sarah

AU - Krammer, Tobias

AU - Leipold, Alexander M.

AU - Hoke, Matthias

AU - Ozsvár-Kozma, Mária

AU - Beneš, Hannah

AU - Schillinger, Martin

AU - Minar, Erich

AU - Roesch, Melanie

AU - Göderle, Laura

AU - Hladik, Anastasiya

AU - Knapp, Sylvia

AU - Colonna, Marco

AU - Martini, Rudolf

AU - Saliba, Antoine Emmanuel

AU - Haass, Christian

AU - Zernecke, Alma

AU - Binder, Christoph J.

AU - Cochain, Clément

PY - 2024/3

Y1 - 2024/3

N2 - Atherosclerosis is a chronic disease of the vascular wall driven by lipid accumulation and inflammation in the intimal layer of arteries, and its main complications—myocardial infarction and stroke—are the leading cause of mortality worldwide1,2. Recent studies have identified triggering receptor expressed on myeloid cells 2 (TREM2), a lipid-sensing receptor regulating myeloid cell functions3, to be highly expressed in macrophage foam cells in experimental and human atherosclerosis4. However, the role of TREM2 in atherosclerosis is not fully known. Here we show that hematopoietic or global TREM2 deficiency increased, whereas TREM2 agonism decreased, necrotic core formation in early atherosclerosis. We demonstrate that TREM2 is essential for the efferocytosis capacities of macrophages and to the survival of lipid-laden macrophages, indicating a crucial role of TREM2 in maintaining the balance between foam cell death and clearance of dead cells in atherosclerotic lesions, thereby controlling plaque necrosis.

AB - Atherosclerosis is a chronic disease of the vascular wall driven by lipid accumulation and inflammation in the intimal layer of arteries, and its main complications—myocardial infarction and stroke—are the leading cause of mortality worldwide1,2. Recent studies have identified triggering receptor expressed on myeloid cells 2 (TREM2), a lipid-sensing receptor regulating myeloid cell functions3, to be highly expressed in macrophage foam cells in experimental and human atherosclerosis4. However, the role of TREM2 in atherosclerosis is not fully known. Here we show that hematopoietic or global TREM2 deficiency increased, whereas TREM2 agonism decreased, necrotic core formation in early atherosclerosis. We demonstrate that TREM2 is essential for the efferocytosis capacities of macrophages and to the survival of lipid-laden macrophages, indicating a crucial role of TREM2 in maintaining the balance between foam cell death and clearance of dead cells in atherosclerotic lesions, thereby controlling plaque necrosis.

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U2 - 10.1038/s44161-024-00429-9

DO - 10.1038/s44161-024-00429-9

M3 - Letter

C2 - 38974464

AN - SCOPUS:85187488682

SN - 2731-0590

VL - 3

SP - 269

EP - 282

JO - Nature Cardiovascular Research

JF - Nature Cardiovascular Research

IS - 3

ER -

TREM2 protects from atherosclerosis by limiting necrotic core formation

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