Piollet Marie, Porsch Florentina, Rizzo Giuseppe, Kapser Frederieke, Schulz Dirk J J, Kiss Máté G, Schlepckow Kai, Morenas-Rodriguez Estrella, Sen Mustafa Orkun, Gropper Julius, Bandi Sourish Reddy, Schäfer Sarah, Krammer Tobias, Leipold Alexander M, Hoke Matthias, Ozsvár-Kozma Mária, Beneš Hannah, Schillinger Martin, Minar Erich, Roesch Melanie, Göderle Laura, Hladik Anastasiya, Knapp Sylvia, Colonna Marco, Martini Rudolf, Saliba Antoine-Emmanuel, Haass Christian, Zernecke Alma, Binder Christoph J, Cochain Clément
Institute of Experimental Biomedicine, University Hospital Würzburg, Würzburg, Germany.
Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
Nat Cardiovasc Res. 2024 Mar;3(3):269-282. doi: 10.1038/s44161-024-00429-9. Epub 2024 Mar 12.
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 functions [3], to be highly expressed in macrophage foam cells in experimental and human atherosclerosis [4]. 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.
动脉粥样硬化是一种血管壁的慢性疾病，由动脉内膜层的脂质积累和炎症驱动，其主要并发症心肌梗死和中风是全球范围内死亡的主要原因[1,2]。最近的研究发现，髓样细胞表达的触发受体2（TREM2），一种调节髓样细胞功能的脂质感应受体[3]，在实验性和人类动脉粥样硬化的巨噬细胞泡沫细胞中高度表达[4]。然而，TREM2在动脉粥样硬化中的作用尚不完全清楚。在这里，我们表明造血或全身性TREM2缺乏会增加，而TREM2激动作用会减少早期动脉粥样硬化中坏死核心的形成。我们证明TREM2对于巨噬细胞的胞葬作用能力以及富含脂质的巨噬细胞的存活至关重要，这表明TREM2在维持动脉粥样硬化病变中泡沫细胞死亡与死细胞清除之间的平衡从而控制斑块坏死方面起着关键作用。
