TREM2 protects from atherosclerosis by limiting necrotic core formation

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. und Cochain, Clément (2024): TREM2 protects from atherosclerosis by limiting necrotic core formation. In: Nature Cardiovascular Research, Bd. 3, Nr. 3: S. 269-282

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin ; Medizin > Adolf-Butenandt-Institut ; Medizin > Munich Cluster for Systems Neurology (SyNergy) ; Medizin > Institut für Schlaganfall- und Demenzforschung (ISD)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2731-0590
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198