Low human and murine Mcl-1 expression leads to a pro-apoptotic plaque phenotype enriched in giant-cells
| Autor: | Saskia C. A. de Jager, Erik A.L. Biessen, Ilze Bot, Lieve Temmerman, You-Wen He, Marion J.J. Gijbels, Ivan Dzhagalov, Theo J.C. Van Berkel, Chris P. M. Reutelingsperger, Margaux A.C. Fontaine, Marijke M. Westra, Martine Bot, Judith C. Sluimer, Han Jin, Aimee Franssen, Bart J.M. van Vlijmen |
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| Přispěvatelé: | RS: Carim - B07 The vulnerable plaque: makers and markers, Pathologie, RS: CARIM - R3 - Vascular biology, Promovendi CD, RS: CARIM - R3.06 - The vulnerable plaque: makers and markers, Moleculaire Genetica, RS: CARIM - R1 - Thrombosis and haemostasis, Biochemie, RS: Carim - B02 Vascular aspects thrombosis and Haemostasis, RS: Carim - V03 Regenerative and reconstructive medicine vascular disease, Medical Biochemistry, ACS - Atherosclerosis & ischemic syndromes, AII - Inflammatory diseases |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Myeloid Cell lcsh:Medicine PROTEIN Apoptosis 030204 cardiovascular system & hematology Giant Cells Mice 0302 clinical medicine hemic and lymphatic diseases Macrophage MACROPHAGES lcsh:Science NEUTROPHILS Multidisciplinary Chemistry INDUCTION DEATH Cell Differentiation 3T3 Cells Immunohistochemistry Lipids Plaque Atherosclerotic Leukemia Phenotype medicine.anatomical_structure Programmed cell death BCL-2 Mice Transgenic Article 03 medical and health sciences medicine Animals Humans General ATHEROSCLEROTIC PLAQUES lcsh:R Atherosclerosis medicine.disease Molecular biology Mice Inbred C57BL 030104 developmental biology Giant cell ARTERIES Myeloid Cell Leukemia Sequence 1 Protein lcsh:Q Bone marrow Gene Deletion |
| Zdroj: | Scientific Reports, 9(1). Nature Publishing Group Scientific Reports, Vol 9, Iss 1, Pp 1-11 (2019) Scientific Reports, 9(1), 14547 Scientific Reports, 9:14547. Nature Publishing Group Scientific Reports Scientific Reports, 9. NATURE PUBLISHING GROUP Scientific reports, 9(1):14547. Nature Publishing Group |
| ISSN: | 2045-2322 |
| Popis: | The anti-apoptotic protein myeloid cell leukemia 1 (Mcl-1) plays an important role in survival and differentiation of leukocytes, more specifically of neutrophils. Here, we investigated the impact of myeloid Mcl-1 deletion in atherosclerosis. Western type diet fed LDL receptor-deficient mice were transplanted with either wild-type (WT) or LysMCre Mcl-1fl/fl (Mcl-1−/−) bone marrow. Mcl-1 myeloid deletion resulted in enhanced apoptosis and lipid accumulation in atherosclerotic plaques. In vitro, Mcl-1 deficient macrophages also showed increased lipid accumulation, resulting in increased sensitivity to lipid-induced cell death. However, plaque size, necrotic core and macrophage content were similar in Mcl-1−/− compared to WT mice, most likely due to decreased circulating and plaque-residing neutrophils. Interestingly, Mcl-1−/− peritoneal foam cells formed up to 45% more multinucleated giant cells (MGCs) in vitro compared to WT, which concurred with an increased MGC presence in atherosclerotic lesions of Mcl-1−/− mice. Moreover, analysis of human unstable atherosclerotic lesions also revealed a significant inverse correlation between MGC lesion content and Mcl-1 gene expression, coinciding with the mouse data. Taken together, these findings suggest that myeloid Mcl-1 deletion leads to a more apoptotic, lipid and MGC-enriched phenotype. These potentially pro-atherogenic effects are however counteracted by neutropenia in circulation and plaque. |
| Databáze: | OpenAIRE |
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