1. T-cell Abca1 and Abcg1 cholesterol efflux pathways suppress T-cell apoptosis and senescence and increase atherosclerosis in middle-agedLdlr-/-mice
- Author
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Venetia Bazioti, Anouk M. La Rose, Sjors Maassen, Frans Bianchi, Rinse de Boer, Emma Guilbaud, Arthur Flohr-Svendsen, Anouk G. Groenen, Alejandro Marmolejo-Garza, Mirjam H. Koster, Niels J. Kloosterhuis, Alle T. Pranger, Miriam Langelaar-Makkinje, Alain de Bruin, Bart van de Sluis, Alison B. Kohan, Laurent Yvan-Charvet, Geert van den Bogaart, and Marit Westerterp
- Subjects
lipids (amino acids, peptides, and proteins) - Abstract
Atherosclerosis is a chronic inflammatory disease driven by hypercholesterolemia. During aging, T-cells accumulate cholesterol, which could lead to a pro-inflammatory phenotype. However, the role of cholesterol efflux pathways mediated by ATP-binding cassette A1 and G1 (ABCA1/ABCG1) in T-cell-dependent age-related inflammation and atherosclerosis remains poorly understood. In this study, we generated mice with T-cell-specificAbca1/Abcg1-deficiency on the low-density-lipoprotein-receptor deficient (Ldlr-/-) background. T-cellAbca1/Abcg1-deficiency decreased blood, lymph node, and splenic T-cells, and increased T-cell activation and apoptosis. T-cellAbca1/Abcg1-deficiency induced a premature T-cell aging phenotype in middle-aged (12-13 months)Ldlr-/-mice, reflected by upregulation of senescence markers. Despite T-cell senescence and enhanced T-cell activation, T-cellAbca1/Abcg1-deficiency decreased atherosclerosis and aortic inflammation in middle-agedLdlr-/-mice, accompanied by decreased T-cells in atherosclerotic plaques. We attribute these effects to T-cell apoptosis downstream of T-cell activation. Collectively, T-cell cholesterol efflux pathways are critical for maintaining T-cell numbers, suppress senescence, and induce atherosclerosis in middle-agedLdlr-/-mice.
- Published
- 2022