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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Mice lacking MERTK or expressing a constitutively inactive MERTK have larger plaques and greater necrotic core area than control mice.
“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]
Impaired macrophage efferocytosis enhances atherogenesis and atherosclerotic plaque instability.
“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]
Cites
Inflammation in atherosclerosis
Libby, P. (2002) · Nature · doi:10.1038/nature01323 · Cited by 8,315 · see citing works
Inflammation in Atherosclerosis
Libby, P. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.179705 · Cited by 3,748 · see citing works
Cardiovascular Medicine at the Turn of the Millennium: Triumphs, Concerns, and Opportunities
D, E. B. M. (1997) · New England Journal of Medicine · doi:10.1056/nejm199711063371906 · Cited by 1,428 · see citing works
Tabas, I., Williams, K. J., & Borén, J. (2007) · Circulation · doi:10.1161/circulationaha.106.676890 · Cited by 1,399 · see citing works
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 · see citing works
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 · see citing works
Yan, J. X., Wait, R., Berkelman, T., Harry, R. A., Westbrook, J. A., Wheeler, C., & Dunn, M. J. (2000) · Electrophoresis · doi:10.1002/1522-2683(200011)21:17 · Cited by 705 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Consequences of cellular cholesterol accumulation: basic concepts and physiological implications
Tabas, I. A. (2002) · Journal of Clinical Investigation · doi:10.1172/jci16452 · Cited by 600 · see citing works
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 · see citing works
Consequences of cellular cholesterol accumulation: basic concepts and physiological implications
Tabas, I. A. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0216452 · Cited by 541 · see citing works
Self-citationPhagocytosis 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 · see citing works
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 · see citing works
Vandivier, R. W., Henson, P. M., & Douglas, I. S. (2006) · CHEST Journal · doi:10.1378/chest.129.6.1673 · Cited by 450 · see citing works
Libby, P. (2005) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.07.006 · Cited by 388 · see citing works
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 349 · see citing works
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 · see citing works
Camenisch, T. D., Koller, B. H., Earp, H. S., & Matsushima, G. K. (1999) · PubMed · Cited by 321 · see citing works
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 · see citing works
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 283 · see citing works
Schrijvers, D. M., DEMEYER, G., HERMAN, A., & Martinet, W. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.09.005 · Cited by 278 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 141 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
Apoptosis and Efferocytosis in Mouse Models of Atherosclerosis
Tabas, I. A. (2007) · Current Drug Targets · doi:10.2174/138945007783220623 · Cited by 75 · see citing works
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 · see citing works
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 · see citing works
(2006) · Canadian Journal of Cardiology · doi:10.1016/s0828-282x(06)70248-3 · Cited by 5 · see citing works
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Macrophages in atherosclerosis: a dynamic balance
Moore, K. J., Sheedy, F. J., & Fisher, E. A. (2013) · Nature reviews. Immunology · doi:10.1038/nri3520 · Cited by 2,559 · see citing works
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 · see citing works
Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities
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 · see citing works
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 · see citing works
Macrophage death and defective inflammation resolution in atherosclerosis
Tabas, I. (2010) · Nature Reviews Immunology · doi:10.1038/nri2675 · Cited by 1,120 · see citing works
Self-citationEfferocytosis in health and disease
Doran, A. C., Yurdagul, A., & Tabas, I. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0240-6 · Cited by 1,066 · see citing works
Self-citationInflammation and plaque vulnerability
Hansson, G. K., Libby, P., & Tabas, I. A. (2015) · Journal of Internal Medicine · doi:10.1111/joim.12406 · Cited by 809 · see citing works
Self-citationCD47-blocking antibodies restore phagocytosis and prevent atherosclerosis
Kojima, Y., Volkmer, J.-P., McKenna, K., Civelek, M., Lusis, A. J., Miller, C. L., Direnzo, D., Nanda, V., Ye, J., Connolly, A. J., et al. (2016) · Nature · doi:10.1038/nature18935 · Cited by 683 · see citing works
A-González, N., Bensinger, S. J., Hong, C., Beceiro, S., Bradley, M. N., Zelcer, N., Deniz, J. M., Ramírez, C. M., Díaz, M., Gallardo, G., et al. (2009) · Immunity · doi:10.1016/j.immuni.2009.06.018 · Cited by 674 · see citing works
Zizzo, G., Hilliard, B. A., Monestier, M., & Cohen, P. L. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1200662 · Cited by 650 · see citing works
Macrophage Autophagy Plays a Protective Role in Advanced Atherosclerosis
Liao, X., Sluimer, J. C., Wang, Y., Subramanian, M., Brown, K., Pattison, J. S., Robbins, J., Martinez, J., & Tabas, I. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.01.022 · Cited by 627 · see citing works
Self-citationLemke, G. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a009076 · Cited by 598 · see citing works
Clearance of apoptotic cells: implications in health and disease
Elliott, M. R., & Ravichandran, K. S. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.201004096 · Cited by 547 · see citing works
Macrophage-targeted nanomedicine for the diagnosis and treatment of atherosclerosis
Chen, W., Schilperoort, M., Cao, Y., Shi, J., Tabas, I. A., & Tao, W. (2021) · Nature Reviews Cardiology · doi:10.1038/s41569-021-00629-x · Cited by 533 · see citing works
Self-citationHeckmann, B. L., Teubner, B. J. W., Tummers, B., Boada-Romero, E., Harris, L., Yang, M., Guy, C. S., Zakharenko, S. S., & Green, D. R. (2019) · Cell · doi:10.1016/j.cell.2019.05.056 · Cited by 503 · see citing works
“Similar effects were observed in response to dying cells in macrophages lacking Rac1 or the efferocytosis receptors merTK and TIM4 (Cai et al., 2018; Camenisch et al., 1999; Martinez et al., 2011; Scott et al., 2001; Thorp et al., 2008), consistent with this idea.”
Regulatory T Cells Promote Macrophage Efferocytosis during Inflammation Resolution
Proto, J. D., Doran, A. C., Gusarova, G., Yurdagul, A., Sozen, E., Subramanian, M., Islam, M. N., Rymond, C. C., Du, J., Hook, J., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.07.015 · Cited by 441 · see citing works
Self-citationMolecular Biology of Atherosclerosis
Hopkins, P. N. (2013) · Physiological Reviews · doi:10.1152/physrev.00004.2012 · Cited by 456 · see citing works
How macrophages deal with death
Lemke, G. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0167-y · Cited by 437 · see citing works
Macrophages and lipid metabolism
Remmerie, A., & Scott, C. L. (2018) · Cellular Immunology · doi:10.1016/j.cellimm.2018.01.020 · Cited by 385 · see citing works
Macrophages: The Good, the Bad, and the Gluttony
Ross, E. A., Devitt, A., & Johnson, J. R. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.708186 · Cited by 436 · see citing works
Fredman, G., Hellmann, J., Proto, J. D., Kuriakose, G., Colas, R. A., Dorweiler, B., Connolly, E. S., Solomon, R., Jones, D. M., Heyer, E. J., et al. (2016) · Nature Communications · doi:10.1038/ncomms12859 · Cited by 411 · see citing works
Self-citationMechanisms and consequences of macrophage apoptosis in atherosclerosis
Seimon, T., & Tabas, I. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r800032-jlr200 · Cited by 411 · see citing works
Self-citationWan, E. Y., Yeap, X. Y., Dehn, S., Terry, R. L., Novak, M. L., Zhang, S., Iwata, S., Han, X., Homma, S., Drosatos, K., et al. (2013) · Circulation Research · doi:10.1161/circresaha.113.301198 · Cited by 385 · see citing works
Self-citationMitochondrial fission promotes the continued clearance of apoptotic cells by macrophages
Wang, Y., Subramanian, M., Yurdagul, A., Barbosa-Lorenzi, V. C., Cai, B., de Juan-Sanz, J., Ryan, T. A., Nomura, M., Maxfield, F. R., & Tabas, I. (2017) · Cell · doi:10.1016/j.cell.2017.08.041 · Cited by 364 · see citing works
Self-citationThorp, E. B., Li, G., Seimon, T. A., Kuriakose, G., Ron, D., & Tabas, I. A. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.03.003 · Cited by 342 · see citing works
Self-citationAtherosclerotic Plaque Destabilization
Silvestre-Roig, C., de Winther, M. P. J., Weber, C., Daemen, M. J. A. P., Lutgens, E., & Soehnlein, O. (2014) · Circulation Research · doi:10.1161/circresaha.114.302355 · Cited by 334 · see citing works
Kyaw, T. S., Tay, C., Krishnamurthi, S., Kanellakis, P., Agrotis, A., Tipping, P. G., Bobik, A., & Toh, B. (2011) · Circulation Research · doi:10.1161/circresaha.111.248542 · Cited by 333 · see citing works
Leukocytes Link Local and Systemic Inflammation in Ischemic Cardiovascular Disease
Libby, P., Nahrendorf, M., & Świrski, F. K. (2016) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2015.12.048 · Cited by 324 · see citing works
The clearance of dying cells: table for two
Green, D. R., Oguin, T. H., & Martinez, J. (2016) · Cell Death & Differentiation · doi:10.1038/cdd.2015.172 · Cited by 314 · see citing works
Mechanisms and Consequences of Defective Efferocytosis in Atherosclerosis
Yurdagul, A., Doran, A. C., Cai, B., Fredman, G., & Tabas, I. A. (2018) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2017.00086 · Cited by 300 · see citing works
Self-citationThorp, E., Vaisar, T., Subramanian, M., Mautner, L., Blobel, C., & Tabas, I. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.263020 · Cited by 298 · see citing works
Self-citationThe role of efferocytosis in atherosclerosis
Kojima, Y., Weissman, I. L., & Leeper, N. J. (2017) · Circulation · doi:10.1161/circulationaha.116.025684 · Cited by 289 · see citing works
A Role of RIP3-Mediated Macrophage Necrosis in Atherosclerosis Development
Lin, J., Li, H., Yang, M. H., Ren, J., Huang, Z., Han, F., Huang, J., Ma, J., Zhang, D., Zhang, Z., et al. (2013) · Cell Reports · doi:10.1016/j.celrep.2012.12.012 · Cited by 266 · see citing works
The role of non-resolving inflammation in atherosclerosis
Kasikara, C., Doran, A. C., Cai, B., & Tabas, I. (2018) · Journal of Clinical Investigation · doi:10.1172/jci97950 · Cited by 266 · see citing works
Self-citationMacrophage MerTK Promotes Liver Fibrosis in Nonalcoholic Steatohepatitis
Cai, B., Dongiovanni, P., Corey, K. E., Wang, X., Shmarakov, I. O., Zheng, Z., Kasikara, C., Davra, V., Meroni, M., Chung, R. T., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2019.11.013 · Cited by 266 · see citing works
Self-citationMerTK receptor cleavage promotes plaque necrosis and defective resolution in atherosclerosis
Cai, B., Thorp, E. B., Doran, A. C., Sansbury, B. E., Daemen, M. J. A. P., Dorweiler, B., Spite, M., Fredman, G., & Tabas, I. (2017) · Journal of Clinical Investigation · doi:10.1172/jci90520 · Cited by 262 · see citing works
Self-citationWang, W., Liu, W., Fidler, T., Wang, Y., Tang, Y., Woods, B., Welch, C., Cai, B., Silvestre-Roig, C., Ai, D., et al. (2018) · Circulation Research · doi:10.1161/circresaha.118.313283 · Cited by 262 · see citing works
Self-citationMerTK cleavage limits proresolving mediator biosynthesis and exacerbates tissue inflammation
Cai, B., Thorp, E. B., Doran, A. C., Subramanian, M., Sansbury, B. E., Lin, C., Spite, M. R., Fredman, G., & Tabas, I. A. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1524292113 · Cited by 253 · see citing works
Self-citationABCA1 and ABCG1 Protect Against Oxidative Stress–Induced Macrophage Apoptosis During Efferocytosis
Yvan-Charvet, L., Pagler, T. A., Seimon, T. A., Thorp, E., Welch, C. L., Witztum, J. L., Tabas, I., & Tall, A. R. (2010) · Circulation Research · doi:10.1161/circresaha.110.217281 · Cited by 217 · see citing works
Self-citationMechanisms and consequences of efferocytosis in advanced atherosclerosis
Thorp, E., & Tabas, I. (2009) · Journal of Leukocyte Biology · doi:10.1189/jlb.0209115 · Cited by 231 · see citing works
Self-citationAtherosclerosis – A matter of unresolved inflammation
Viola, J. R., & Soehnlein, O. (2015) · Seminars in Immunology · doi:10.1016/j.smim.2015.03.013 · Cited by 227 · see citing works
Macrophage Apoptosis and Efferocytosis in the Pathogenesis of Atherosclerosis
Linton, M. F., Babaev, V. R., Huang, J., Linton, E. F., Tao, H., & Yancey, P. G. (2016) · Circulation Journal · doi:10.1253/circj.cj-16-0924 · Cited by 225 · see citing works
de Jager, S. C. A., Bermúdez, B., Bot, I., Koenen, R. R., Bot, M., Kavelaars, A., de Waard, V., Heijnen, C. J., Muriana, F. J. G., Weber, C., et al. (2011) · The Journal of Experimental Medicine · doi:10.1084/jem.20100370 · Cited by 222 · see citing works
Kamaly, N., Fredman, G., Fojas, J. J. R., Subramanian, M., Choi, W. I., Zepeda, K., Vilos, C., Yu, M., Gadde, S., Wu, J., et al. (2016) · ACS Nano · doi:10.1021/acsnano.6b01114 · Cited by 220 · see citing works
Self-citationClarke, M. C. H., Talib, S., Figg, N. L., & Bennett, M. R. (2010) · Circulation Research · doi:10.1161/circresaha.109.208389 · Cited by 216 · see citing works
Carcinogenesis: Failure of resolution of inflammation?
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Programmed death of macrophages in atherosclerosis: mechanisms and therapeutic targets
Meyer, G. R. Y. D., Zurek, M., Puylaert, P., & Martinet, W. (2024) · Nature Reviews Cardiology · doi:10.1038/s41569-023-00957-0 · Cited by 214 · see citing works
Canfrán‐Duque, A., Rotllán, N., Zhang, X., Fernández‐Fuertes, M., Ramírez, C. M., Araldi, E., Daimiel, L., Busto, R., Fernandez-Hernando, C. F., & Suárez, Y. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201607492 · Cited by 203 · see citing works
Apoptotic Cell Death and Efferocytosis in Atherosclerosis
Vré, E. A. V., Ait‐Oufella, H., Tedgui, A., & Mallat, Z. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.224873 · Cited by 200 · see citing works
Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases
Song, P., An, J., & Zou, M.-H. (2020) · Cells · doi:10.3390/cells9030671 · Cited by 198 · see citing works
Schrijvers, D. M., Meyer, G. R. Y. D., & Martinet, W. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.224899 · Cited by 189 · see citing works
Self-citationOvermeire, E. V., Laoui, D., Keirsse, J., Ginderachter, J. A. V., & Sarukhan, A. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00127 · Cited by 182 · see citing works
Cai, B., Kasikara, C., Doran, A. C., Ramakrishnan, R., Birge, R. B., & Tabas, I. (2018) · Science Signaling · doi:10.1126/scisignal.aar3721 · Cited by 175 · see citing works
Self-citationBoosting Inflammation Resolution in Atherosclerosis
Fredman, G., & Tabas, I. A. (2017) · American Journal Of Pathology · doi:10.1016/j.ajpath.2017.01.018 · Cited by 173 · see citing works
Self-citationA macrophage-specific lncRNA regulates apoptosis and atherosclerosis by tethering HuR in the nucleus
Simion, V., Zhou, H., Haemmig, S., Pierce, J. B., Mendes, S., Tesmenitsky, Y., Pérez‐Cremades, D., Lee, J. F., Chen, A. F., Ronda, N., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19664-2 · Cited by 173 · see citing works
Botts, S. R., Fish, J. E., & Howe, K. L. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.787541 · Cited by 172 · see citing works
Johnson, J. L., Devel, L., Czarny, B., George, S. J., Jackson, C. L., Rogakos, V., Beau, F., Yiotakis, A., Newby, A. C., & Dive, V. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.219147 · Cited by 171 · see citing works
Macrophage LRP-1 Controls Plaque Cellularity by Regulating Efferocytosis and Akt Activation
Yancey, P. G., Blakemore, J., Ding, L., Fan, D., Overton, C. D., Zhang, Y., Linton, M. F., & Fazio, S. (2010) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.109.202051 · Cited by 168 · see citing works
Li, S., Sun, Y., Liang, C., Thorp, E. B., Han, S., Jehle, A. W., Saraswathi, V., Pridgen, B. C., Kanter, J. E., Li, R., et al. (2009) · Circulation Research · doi:10.1161/circresaha.109.199570 · Cited by 168 · see citing works
Self-citationCytokine Circuits in Cardiovascular Disease
Williams, J. W., Huang, L.-H., & Randolph, G. J. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.007 · Cited by 166 · see citing works
Efferocytosis in atherosclerosis
Adkar, S. S., & Leeper, N. J. (2024) · Nature Reviews Cardiology · doi:10.1038/s41569-024-01037-7 · Cited by 166 · see citing works
Treg-mediated suppression of atherosclerosis requires MYD88 signaling in DCs
Subramanian, M., Thorp, E. B., Hansson, G. K., & Tabas, I. A. (2012) · Journal of Clinical Investigation · doi:10.1172/jci64617 · Cited by 163 · see citing works
Self-citationMacrophages in vascular inflammation and atherosclerosis
Cochain, C., & Zernecke, A. (2017) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-017-1941-y · Cited by 164 · see citing works
Efficient Phagocytosis Requires Triacylglycerol Hydrolysis by Adipose Triglyceride Lipase
Chandak, P. G., Radović, B., Aflaki, E., Kolb, D., Buchebner, M., Fröhlich, E., Magnes, C., Sinner, F., Haemmerle, G., Zechner, R., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.107854 · Cited by 163 · see citing works
Self-citationFredman, G., & Serhan, C. N. (2024) · Nature Reviews Cardiology · doi:10.1038/s41569-023-00984-x · Cited by 160 · see citing works
The role of phosphatidylserine recognition receptors in multiple biological functions
Naeini, M. B., Bianconi, V., Pirro, M., & Sahebkar, A. (2020) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-020-00214-z · Cited by 156 · see citing works
PFKFB2-mediated glycolysis promotes lactate-driven continual efferocytosis by macrophages
Schilperoort, M., Ngai, D., Katerelos, M., Power, D., & Tabas, I. (2023) · Nature Metabolism · doi:10.1038/s42255-023-00736-8 · Cited by 145 · see citing works
Self-citationM2 Macrophages as a Potential Target for Antiatherosclerosis Treatment
Bi, Y., Chen, J., Hu, F., Liu, J., Li, M., & Zhao, L. (2019) · Neural Plasticity · doi:10.1155/2019/6724903 · Cited by 153 · see citing works
The walking dead: macrophage inflammation and death in atherosclerosis
Kavurma, M. M., Rayner, K. J., & Karunakaran, D. (2017) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000394 · Cited by 145 · see citing works
Jin, Y. H., Liu, Y., Xu, L., Xu, J., Xiong, Y., Peng, Y., Ding, K., Zheng, S., Yang, N., Zhang, Z., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04966-8 · Cited by 145 · see citing works
Necrotic cell death in atherosclerosis
Martinet, W., Schrijvers, D. M., & Meyer, G. R. Y. D. (2011) · Basic Research in Cardiology · doi:10.1007/s00395-011-0192-x · Cited by 141 · see citing works
Self-citationEfferocytosis and Its Role in Inflammatory Disorders
Ge, Y., Huang, M., & Yao, Y.-M. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.839248 · Cited by 139 · see citing works
Efferocytosis in atherosclerotic lesions: Malfunctioning regulatory pathways and control mechanisms
Tajbakhsh, A., Rezaee, M., Kovanen, P. T., & Sahebkar, A. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.02.003 · Cited by 134 · see citing works
González, L., & Trigatti, B. L. (2016) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2016.12.010 · Cited by 130 · see citing works
Macrophages and Cardiovascular Health
Frodermann, V., & Nahrendorf, M. (2018) · Physiological Reviews · doi:10.1152/physrev.00068.2017 · Cited by 126 · see citing works
Canfrán‐Duque, A., Rotllán, N., Zhang, X., Andrés‐Blasco, I., Thompson, B. M., Sun, J., Price, N. L., Fernández‐Fuertes, M., Fowler, J. W., Gómez‐Coronado, D., et al. (2022) · Circulation · doi:10.1161/circulationaha.122.059062 · Cited by 127 · see citing works
The phosphatidylserine receptor TIM4 utilizes integrins as coreceptors to effect phagocytosis
Flannagan, R. S., Canton, J., Furuya, W., Glogauer, M., & Grinstein, S. (2014) · Molecular Biology of the Cell · doi:10.1091/mbc.e13-04-0212 · Cited by 126 · see citing works
Kasikara, C., Davra, V., Calianese, D. C., Geng, K., Spires, T. E., Quigley, M. M., Wichroski, M. J., Sriram, G., Suárez-López, L., Yaffe, M. B., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-2614 · Cited by 125 · see citing works
Luo, Y., Sun, G., Dong, X., Wang, M., Qin, M., Yu, Y., & Sun, X. (2015) · PLoS ONE · doi:10.1371/journal.pone.0120259 · Cited by 124 · see citing works
Impaired Clearance of Apoptotic Cells in Chronic Inflammatory Diseases: Therapeutic Implications
Szondy, Z., Garabuczi, Ã., Joós, G., Tsay, G. J., & Sarang, Z. (2014) · Frontiers in Immunology · doi:10.3389/fimmu.2014.00354 · Cited by 124 · see citing works
The Impact of Macrophage Insulin Resistance on Advanced Atherosclerotic Plaque Progression
Tabas, I. A., Tall, A. R., & Accili, D. (2010) · Circulation Research · doi:10.1161/circresaha.109.208488 · Cited by 123 · see citing works
Self-citationAn AXL/LRP-1/RANBP9 complex mediates DC efferocytosis and antigen cross-presentation in vivo
Subramanian, M., Hayes, C. D., Thome, J. J. C., Thorp, E. B., Matsushima, G. K., Herz, J., Färber, D. L., Liu, K., Lakshmana, M. K., & Tabas, I. A. (2014) · Journal of Clinical Investigation · doi:10.1172/jci72051 · Cited by 123 · see citing works
Self-citationSuleiman, L., Négrier, C., & Boukerche, H. (2013) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2013.07.004 · Cited by 120 · see citing works
Petri, M. H., Laguna‐Fernandez, A., Arnardottir, H., Wheelock, C. E., Perretti, M., Hansson, G. K., & Bäck, M. (2017) · British Journal of Pharmacology · doi:10.1111/bph.13707 · Cited by 120 · see citing works
Seneviratne, A. N., Edsfeldt, A., Cole, J. E., Kassiteridi, C., Swart, M., Park, I., Green, P., Khoyratty, T., Saliba, D., Goddard, M. E., et al. (2017) · Circulation · doi:10.1161/circulationaha.117.027844 · Cited by 117 · see citing works
Yamamoto, S., Yancey, P. G., Zuo, Y., Ma, L.-J., Kaseda, R., Fogo, A. B., Ichikawa, I., Linton, M. F., Fazio, S., & Kon, V. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.237198 · Cited by 115 · see citing works
Resolvin D1 promotes efferocytosis in aging by limiting senescent cell‐induced MerTK cleavage
Rymut, N., Heinz, J., Sadhu, S., Hosseini, Z., Riley, C. O., Marinello, M., Maloney, J., MacNamara, K. C., Spite, M. R., & Fredman, G. (2019) · The FASEB Journal · doi:10.1096/fj.201902126r · Cited by 113 · see citing works
Macrophage EP4 Deficiency Increases Apoptosis and Suppresses Early Atherosclerosis
Babaev, V. R., Chew, J. D., Ding, L., Davis, S., Breyer, M. D., BREYER, R. M., Oates, J. A., Fazio, S., & Linton, M. F. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.09.005 · Cited by 113 · see citing works
Doran, A. C., Özcan, L., Cai, B., Zheng, Z., Fredman, G., Rymond, C. C., Dorweiler, B., Sluimer, J. C., Hsieh, J., Kuriakose, G., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci94735 · Cited by 113 · see citing works
Self-citationZizzo, G., & Cohen, P. (2015) · Journal of Inflammation · doi:10.1186/s12950-015-0081-4 · Cited by 94 · see citing works
Malondialdehyde Epitopes as Targets of Immunity and the Implications for Atherosclerosis
Papac-Miličević, N., Busch, C. J., & Binder, C. J. (2016) · Advances in immunology · doi:10.1016/bs.ai.2016.02.001 · Cited by 109 · see citing works
The Role of Lipids and Lipoproteins in Atherosclerosis
Linton, M. F., Yancey, P. G., Davies, S. S., Jerome, W. G., Linton, E. F., Song, W., Doran, A. C., & Vickers, K. C. (2015) · Europe PMC (PubMed Central) · Cited by 108 · see citing works
Thorp, E., Subramanian, M., & Tabas, I. (2011) · European Journal of Immunology · doi:10.1002/eji.201141719 · Cited by 107 · see citing works
Self-citationXian, X., Ding, Y., Dieckmann, M., Zhou, L., Plattner, F., Liu, M., Parks, J. S., Hammer, R. E., Boucher, P., Tsai, S. X., et al. (2017) · eLife · doi:10.7554/elife.29292 · Cited by 103 · see citing works
Emerging Role of Mast Cells and Macrophages in Cardiovascular and Metabolic Diseases
Xu, J., & Shi, G. (2012) · Endocrine Reviews · doi:10.1210/er.2011-0013 · Cited by 103 · see citing works
Growth Arrest-Specific Gene 6 (gas6) and Vascular Hemostasis
Laurance, S., Lemarié, C. A., & Blostein, M. D. (2012) · Advances in Nutrition · doi:10.3945/an.111.001826 · Cited by 101 · see citing works
Efferocytosis: molecular mechanisms and pathophysiological perspectives
Hayat, S. M. G., Bianconi, V., Pirro, M., & Sahebkar, A. (2018) · Immunology and Cell Biology · doi:10.1111/imcb.12206 · Cited by 97 · see citing works
Davra, V., Kumar, S., Geng, K., Calianese, D. C., Mehta, D., Gadiyar, V., Kasikara, C., Lahey, K. C., Chang, Y., Wichroski, M. J., et al. (2020) · Cancer Research · doi:10.1158/0008-5472.can-20-2066 · Cited by 96 · see citing works
Wang, H., Yang, Y., Sun, X., Tian, F., Guo, S., Wang, W., Tian, Z., Jin, H. H., Zhang, Z., & Tian, Y. (2018) · Theranostics · doi:10.7150/thno.26193 · Cited by 95 · see citing works
Werfel, T. A., Elion, D. L., Rahman, B., Hicks, D. J., Sanchez, V. M., Ericsson, P. I. G., Nixon, M. J., James, J. L., Balko, J. M., Scherle, P., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-1106 · Cited by 92 · see citing works
- 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
- Health Sciences › Medicine › Surgery › 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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