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Mertk Receptor Mutation Reduces Efferocytosis Efficiency and Promotes Apoptotic Cell Accumulation and Plaque Necrosis in Atherosclerotic Lesions of Apoe −/− Mice
Open accessAbstract
Objective— Atherosclerotic plaques that are prone to disruption and acute thrombotic vascular events are characterized by large necrotic cores. Necrotic cores result from the combination of macrophage apoptosis and defective phagocytic clearance (efferocytosis) of these apoptotic cells. We previously showed that macrophages with tyrosine kinase-defective Mertk receptor (Mertk KD ) have a defect in phagocytic clearance of apoptotic macrophages in vitro. Herein we test the hypothesis that the Mertk KD mutation would result in increased accumulation of apoptotic cells and promote necrotic core expansion in a mouse model of advanced atherosclerosis. Methods and Results— Mertk KD ; Apoe −/− mice and control Apoe −/− mice were fed a Western-type diet for 10 or 16 weeks, and aortic root lesions were analyzed for apoptosis and plaque necrosis. We found that the plaques of the Mertk KD ; Apoe −/− mice had a significant increase in terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive apoptotic cells. Most importantly, there were more non-macrophage-associated apoptotic cells in the Mertk KD lesions, consistent with defective efferocytosis. The more advanced (16-week) Mertk KD ; Apoe −/− plaques were more necrotic, consistent with a progression from apoptotic cell accumulation to plaque necrosis in the setting of a defective efferocytosis receptor. Conclusion— In a mouse model of advanced atherosclerosis, mutation of the phagocytic Mertk receptor promotes the accumulation of apoptotic cells and the formation of necrotic plaques. These data are consistent with the notion that a defect in an efferocytosis receptor can accelerate the progression of atherosclerosis and suggest a novel therapeutic target to prevent advanced plaque progression and its clinical consequences.
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“Conversely, mice lacking MERTK or expressing a constitutively inactive form of MERTK show larger plaque size and increased necrotic core area compared with control mice196,197.”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [196]
In the citing paper
“The impaired ability of macrophage efferocytosis would enhance atherogenesis [139,140,141] and atherosclerotic plaque instability [142,143,144].”
From Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases (2020) · cites this paper as [143]
Citations
Cites
Inflammation in atherosclerosis
Libby, P. (2002) · Nature · doi:10.1038/nature01323 · Cited by 8,315
Inflammation in Atherosclerosis
Libby, P. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.179705 · Cited by 3,796
Cardiovascular Medicine at the Turn of the Millennium: Triumphs, Concerns, and Opportunities
Braunwald, E. (1997) · New England Journal of Medicine · doi:10.1056/nejm199711063371906 · Cited by 1,426
Tabas, I., Williams, K. J., & Borén, J. (2007) · Circulation · doi:10.1161/circulationaha.106.676890 · Cited by 1,399
Self-citationPhagocytosis and clearance of apoptotic cells is mediated by MER
Scott, R. S., McMahon, E. J., Pop, S. M., Reap, E. A., Caricchio, R., Cohen, P. L., Earp, H. S., & Matsushima, G. K. (2001) · Nature · doi:10.1038/35075603 · Cited by 1,215
Taylor, P. R., Carugati, A., Fadok, V. A., Cook, H. T., Andrews, M., Carroll, M. C., Savill, J., Henson, P. M., Botto, M., & Walport, M. J. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.3.359 · Cited by 724
Clarke, M. C. H., Figg, N. L., Maguire, J. J., Davenport, A. P., Goddard, M. J., Littlewood, T. D., & Bennett, M. R. (2006) · Nature Medicine · doi:10.1038/nm1459 · Cited by 645
Consequences and Therapeutic Implications of Macrophage Apoptosis in Atherosclerosis
Tabas, I. A. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000184783.04864.9f · Cited by 641
Self-citationCohen, P. L., Caricchio, R., Abraham, V., Camenisch, T. D., Jennette, J. C., Roubey, R. A. S., Earp, H. S., Matsushima, G. K., & Reap, E. A. (2002) · The Journal of Experimental Medicine · doi:10.1084/jem.20012094 · Cited by 637
Consequences of cellular cholesterol accumulation: basic concepts and physiological implications
Tabas, I. A. (2002) · Journal of Clinical Investigation · doi:10.1172/jci16452 · Cited by 608
Self-citationConsequences of cellular cholesterol accumulation: basic concepts and physiological implications
Tabas, I. A. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0216452 · Cited by 553
Self-citationNagata, K., Ohashi, K., Nakano, T., Arita, H., Zong, C., Hanafusa, H., & Mizuno, K. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.47.30022 · Cited by 541
Phagocytosis of apoptotic cells by macrophages is impaired in atherosclerosis
Schrijvers, D. M., De Meyer, G. R. Y., Kockx, M. M., Herman, A. G., & Martinet, W. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000166517.18801.a7 · Cited by 509
Self-citationVulnerable Plaque: The Pathology of Unstable Coronary Lesions
Virmani, R., BURKE, A. P., Kolodgie, F. D., & Farb, A. A. (2002) · Journal of Interventional Cardiology · doi:10.1111/j.1540-8183.2002.tb01087.x · Cited by 481
Vandivier, R. W., Henson, P. M., & Douglas, I. S. (2006) · CHEST Journal · doi:10.1378/chest.129.6.1673 · Cited by 450
Libby, P. (2005) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.07.006 · Cited by 388
Frequency and Distribution of Thin-Cap Fibroatheroma and Ruptured Plaques in Human Coronary Arteries
Cheruvu, P. K., Finn, A. V., Gardner, C. M., Caplan, J. D., Goldstein, J. A., Stone, G. W., Virmani, R., & Muller, J. E. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.04.086 · Cited by 347
Sather, S., Kenyon, K. D., Lefkowitz, J. B., Liang, X., Varnum, B. C., Henson, P. M., & Graham, D. K. (2006) · Blood · doi:10.1182/blood-2006-05-021634 · Cited by 333
Camenisch, T. D., Koller, B. H., Earp, H. S., & Matsushima, G. K. (1999) · PubMed · Cited by 321
Loss of Akt1 Leads to Severe Atherosclerosis and Occlusive Coronary Artery Disease
Fernandez-Hernando, C. F., Ackah, E., Yu, J., Suárez, Y., Murata, T., Iwakiri, Y., Prendergast, J., Miao, R. Q., Birnbaum, M. J., & Sessa, W. C. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.10.007 · Cited by 292
Camenisch, T. D., Koller, B. H., Earp, H. S., & Matsushima, G. K. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.6.3498 · Cited by 290
Schrijvers, D. M., DEMEYER, G., HERMAN, A., & Martinet, W. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.09.005 · Cited by 275
Self-citationLactadherin Deficiency Leads to Apoptotic Cell Accumulation and Accelerated Atherosclerosis in Mice
Ait-Oufella, H., Kinugawa, K., Zoll, J., Simon, T., Boddaert, J., Heeneman, S., Blanc-Brude, O., Barateau, V., Potteaux, S., Merval, R., et al. (2007) · Circulation · doi:10.1161/circulationaha.106.662080 · Cited by 255
Potter, P. K., Cortés-Hernández, J., Quartier, P., Botto, M., & Walport, M. J. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.6.3223 · Cited by 167
Complement C1q Reduces Early Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice
Bhatia, V. K., Yun, S., Leung, V. W. Y., Grimsditch, D. C., Benson, G. M., Botto, M., Boyle, J. J., & Haskard, D. O. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2007.060406 · Cited by 166
Impaired Clearance of Apoptotic Cells Promotes Synergy between Atherogenesis and Autoimmune Disease
Aprahamian, T. R., Rifkin, I. R., Bonegio, R. G. B., Hugel, B., Freyssinet, J., Sato, K., Castellot, J. J., & Walsh, K. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20031557 · Cited by 163
Feng, B., Zhang, D., Kuriakose, G., Devlin, C. M., Kockx, M. M., & Tabas, I. A. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1732494100 · Cited by 148
Self-citationLim, W.-S., Timmins, J. M., Seimon, T. A., Sadler, A. J., Kolodgie, F. D., Virmani, R., & Tabas, I. A. (2008) · Circulation · doi:10.1161/circulationaha.107.711275 · Cited by 147
Self-citationMorphological characteristics of coronary atherosclerosis in diabetes mellitus
Virmani, R., BURKE, A. P., & Kolodgie, F. D. (2006) · Canadian Journal of Cardiology · doi:10.1016/s0828-282x(06)70991-6 · Cited by 96
Leukocyte Transglutaminase 2 Expression Limits Atherosclerotic Lesion Size
Boisvert, W. A., Rose, D. M., Boullier, A., Quehenberger, O., Sydlaske, A. D., Johnson, K. A., Curtiss, L. K., & Terkeltaub, R. A. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000203503.82693.c1 · Cited by 95
Li, Y., Gerbod-Giannone, M.-C., Seitz, H., Cui, D., Thorp, E. B., Tall, A. R., Matsushima, G. K., & Tabas, I. A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m510579200 · Cited by 91
Self-citationCanault, M., Peiretti, F., Kopp, F., Bonardo, B., Bonzi, M.-F., Coudeyre, J.-C., Alessi, M., Juhan-Vague, I., & Nalbone, G. (2005) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2005.08.031 · Cited by 90
Melaragno, M. G., Fridell, Y.-W. C., & Berk, B. C. (1999) · Trends in Cardiovascular Medicine · doi:10.1016/s1050-1738(00)00027-x · Cited by 87
Apoptosis and Efferocytosis in Mouse Models of Atherosclerosis
Tabas, I. A. (2007) · Current Drug Targets · doi:10.2174/138945007783220623 · Cited by 75
Self-citationCui, D., Thorp, E., Li, Y., Wang, N., Yvan-Charvet, L., Tall, A. R., & Tabas, I. (2007) · Journal of Leukocyte Biology · doi:10.1189/jlb.0307192 · Cited by 73
Self-citationMERTK polymorphisms associated with risk of haematological disorders among Korean SLE patients
Cheong, H. S., Lee, S. O., Choi, C., Sung, Y., Shin, H. D., & Bae, S. (2006) · Lara D. Veeken · doi:10.1093/rheumatology/kel182 · Cited by 24
Ricci, U., Sani, I., Guarducci, S., Biondi, C., Pelagatti, S., Lazzerini, V., Brusaferri, A., Lapini, M., Andreucci, E., Giunti, L., et al. (2000) · Electrophoresis · doi:10.1002/1522-2683(200011)21:17 · Cited by 23
(2006) · Canadian Journal of Cardiology · doi:10.1016/s0828-282x(06)70248-3 · Cited by 5
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Moore, K. J., Sheedy, F. J., & Fisher, E. A. (2013) · Nature reviews. Immunology · doi:10.1038/nri3520 · Cited by 2,559
Borén, J., Chapman, M. J., Krauss, R. M., Packard, C. J., Bentzon, J. F., Binder, C. J., Daemen, M. J., Demer, L. L., Hegele, R. A., Nicholls, S. J., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz962 · Cited by 1,601
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Bäck, M., Yurdagul, A., Tabas, I., Öörni, K., & Kovanen, P. T. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-019-0169-2 · Cited by 1,341
Self-citationApoptotic cell clearance: basic biology and therapeutic potential
Poon, I. K. H., Lucas, C. D., Rossi, A. G., & Ravichandran, K. S. (2014) · Nature Reviews Immunology · doi:10.1038/nri3607 · Cited by 1,223
Macrophage death and defective inflammation resolution in atherosclerosis
Tabas, I. (2010) · Nature Reviews Immunology · doi:10.1038/nri2675 · Cited by 1,120
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Metadata
- Authors
- Thorp, E., Cui, D., Schrijvers, D. M., Kuriakose, G., & Tabas, I.
- Affiliations
- Columbia University (US)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2008-08
- Volume
- 28
- Issue
- 8
- Pages
- 1421-1428
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- PMC
- PMC2575060
- OpenAlex
- W2122693935
- Cited by
- 357
- References
- 38
- Citations by year
- 2026: 22 · 2025: 16 · 2024: 25 · 2023: 13 · 2022: 19 · 2021: 21 · 2020: 24 · 2019: 22 · 2018: 25 · 2017: 26 · 2016: 22 · 2015: 19 · 2014: 19 · 2013: 23 · 2012: 19
- FWCI
- 5.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-75662, P01HL054591, R01HL075662, HL 54591)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Keywords
- efferocytosis, macrophage apoptosis, ApoE-deficient mice, plaque progression, Western diet, aortic root lesions, therapeutic target
- MeSH terms
- c-Mer Tyrosine Kinase, Animals, Aorta, Apolipoproteins E, Disease Models, Animal, Foam Cells, Male, Mutation, Phagocytosis, Proto-Oncogene Proteins, Apoptosis, Mice, Knockout, In Situ Nick-End Labeling, Receptor Protein-Tyrosine Kinases, Atherosclerosis, Mice
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