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Complement factor H binds malondialdehyde epitopes and protects from oxidative stress
Open accessAbstract
Oxidative stress and enhanced lipid peroxidation are linked to many chronic inflammatory diseases, including age-related macular degeneration (AMD). AMD is the leading cause of blindness in Western societies, but its aetiology remains largely unknown. Malondialdehyde (MDA) is a common lipid peroxidation product that accumulates in many pathophysiological processes, including AMD. Here we identify complement factor H (CFH) as a major MDA-binding protein that can block both the uptake of MDA-modified proteins by macrophages and MDA-induced proinflammatory effects in vivo in mice. The CFH polymorphism H402, which is strongly associated with AMD, markedly reduces the ability of CFH to bind MDA, indicating a causal link to disease aetiology. Our findings provide important mechanistic insights into innate immune responses to oxidative stress, which may be exploited in the prevention of and therapy for AMD and other chronic inflammatory diseases.
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“Oxidative stress adducts and components of the complement system have been found to accumulate in drusen and sub-RPE deposits of patients with AMD (Weismann et al., 2011; Shaw et al., 2012), and mice with mutations making them prone to oxidative stress or dysregulation of the complement pathway have been presented as models of AMD (Imamura et al., 2006; Justilien et al., 2007; Hollyfield et al., 2”
From Microtubule motors transport phagosomes in the RPE, and lack of KLC1 leads to AMD-like pathogenesis (2015) · cites this paper as Weismann et al., 2011
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Cites
Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes
Esterbauer, H., Schaur, R. J., & Zollner, H. (1991) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(91)90192-6 · Cited by 6,672
Complement factor H polymorphism in age-related macular degeneration
Klein, R. J., Zeiss, C., Chew, E. Y., Tsai, J.-Y., Sackler, R. S., Haynes, C., Henning, A. K., SanGiovanni, J. P., Mane, S. M., Mayne, S. T., et al. (2005) · Science · doi:10.1126/science.1109557 · Cited by 4,492
Complement factor H polymorphism and age-related macular degeneration
Edwards, A. O., Ritter, R., Abel, K. J., Manning, A., Panhuysen, C., & Farrer, L. A. (2005) · Science · doi:10.1126/science.1110189 · Cited by 2,449
Complement factor H variant increases the risk of age-related macular degeneration
Haines, J. L., Hauser, M. A., Schmidt, S., Scott, W. K., Olson, L. M., Gallins, P., Spencer, K. L., Kwan, S. Y., Noureddine, M., Gilbert, J. R., et al. (2005) · Science · doi:10.1126/science.1110359 · Cited by 2,424
Hageman, G. S., Anderson, D. H., Johnson, L. V., Hancox, L. S., Taiber, A. J., Hardisty, L. I., Hageman, J. L., Stockman, H. A., Borchardt, J. D., Gehrs, K. M., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501536102 · Cited by 1,961
A blast from the past: clearance of apoptotic cells regulates immune responses
Savill, J., Dransfield, I., Gregory, C. D., & Haslett, C. (2002) · Nature reviews. Immunology · doi:10.1038/nri957 · Cited by 1,574
Age-related macular degeneration
Jager, R. D., Mieler, W. F., & Miller, J. W. (2008) · New England Journal of Medicine · doi:10.1056/nejmra0801537 · Cited by 1,379
Complement regulators and inhibitory proteins
Zipfel, P. F., & Skerka, C. (2009) · Nature reviews. Immunology · doi:10.1038/nri2620 · Cited by 1,268
Age-related macular degeneration
de Jong, P. T. V. M. (2006) · New England Journal of Medicine · doi:10.1056/nejmra062326 · Cited by 787
Age-related Macular Degeneration Histopathologic Studies
Green, W. R., & Enger, C. (1993) · Ophthalmology · doi:10.1016/s0161-6420(93)31466-1 · Cited by 757
Cited by
Sorted by citations
Ayala, A., Muñoz, M., & Argüelles, S. (2014) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2014/360438 · Cited by 6,837
“adducts with FH can block both the uptake ofMDA-modified proteins by macrophages and MDA-induced proinflammatory effects in vivo in mice [184]; MDA adducts or MAA adducts can promote binding of complement; (iii) anaphylatoxin C3a (proinflammatory complement components) with oxidatively modified low-density lipoprotein…”
BackgroundComplement System Part I – Molecular Mechanisms of Activation and Regulation
Merle, N. S., Church, S. E., Fremeaux-Bacchi, V., & Roumenina, L. T. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00262 · Cited by 1,620
“Y402H binds more weakly to MDA and oxidized phospholipids expressed on retinal pigment epithelium compared to the non-mutated protein (198, 200).”
BackgroundComplement System Part II: Role in Immunity
Merle, N. S., Noé, R., Halbwachs‐Mecarelli, L., Frémeaux‐Bacchi, V., & Roumenina, L. T. (2015) · Frontiers in Immunology · doi:10.3389/fimmu.2015.00257 · Cited by 1,113
“At risk, FH variant H402 has a weaker capacity to interact with oxidized lipids and malondialdehyde in the drusen, thus allowing constant background complement activation, leading to retinal epithelial cells damage and macrophages activation (249, 250).”
BackgroundBhutto, I. A., & Lutty, G. A. (2012) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.04.005 · Cited by 1,028
“Weismann and associates have demonstrated that CFH binds malondialdehyde epitopes and protects against oxidative stress (Weismann et al., 2011).”
BackgroundAge-related macular degeneration
Fleckenstein, M., Keenan, T. D. L., Guymer, R. H., Chakravarthy, U., Schmitz-Valckenberg, S., Klaver, C. C. W., Wong, W. T., & Chew, E. Y. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-021-00265-2 · Cited by 1,093
The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD
Datta, S., Cano, M., Ebrahimi, K. B., Wang, L., & Handa, J. T. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2017.03.002 · Cited by 843
“The Binder lab, with our collaboration, showed that CFH, mediated through SCR7 and SCR20, binds to MDA, which is contained in oxidized LDL (Weismann et al., 2011).”
BackgroundInfluentialInflammation and its role in age-related macular degeneration
Kauppinen, A., Paterno, J. J., Błasiak, J., Salminen, A., & Kaarniranta, K. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2147-8 · Cited by 683
“MDA is common lipid peroxidation product that forms protein adducts capable of inducing inflammation and RPE damage [114, 115].”
BackgroundImmunology of age-related macular degeneration
Ambati, J., Atkinson, J. P., & Gelfand, B. D. (2013) · Nature reviews. Immunology · doi:10.1038/nri3459 · Cited by 606
Complement in disease: a defence system turning offensive
Ricklin, D., Reis, E. S., & Lambris, J. D. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.70 · Cited by 558
Retinal microglia: Just bystander or target for therapy?
Karlstetter, M., Scholz, R., Rutar, M., Wong, W. T., Provis, J. M., & Langmann, T. (2014) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2014.11.004 · Cited by 570
Complement in Immune and Inflammatory Disorders: Pathophysiological Mechanisms
Ricklin, D., & Lambris, J. D. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1203487 · Cited by 480
“Although questions about disease triggers and the role of systemic versus locally produced complement remain controversial (36), a recent study suggested a contribution of the oxidative stress adduct malondialdehyde as initiator and provided a functional explanation about the disease correlation of the FH Y402H polymo…”
BackgroundInnate sensing of oxidation-specific epitopes in health and disease
Binder, C. J., Papac-Milicevic, N., & Witztum, J. L. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.63 · Cited by 403
Self-citationHolz, F. G., Strauss, E. C., Schmitz-Valckenberg, S., & Campagne, M. V. L. (2014) · Ophthalmology · doi:10.1016/j.ophtha.2013.11.023 · Cited by 404
Animal models of age related macular degeneration
Pennesi, M. E., Neuringer, M., & Courtney, R. J. (2012) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.06.003 · Cited by 391
“For example, the Y402H polymorphism in complement factor H results in a reduced ability of this protein to bind to malondialdehyde, a product of lipid peroxidation which is present in AMD (Weismann et al., 2011).”
BackgroundMechanisms of age‐related macular degeneration and therapeutic opportunities
van Lookeren Campagne, M., LeCouter, J., Yaspan, B. L., & Ye, W. (2014) · The Journal of Pathology · doi:10.1002/path.4266 · Cited by 382
“Of interest, the CFH polymorphism Y402, which is strongly associated with AMD risk, markedly reduces the ability of CFH to bind to MDA [89], providing mechanistic insight into the causal genetic link.”
BackgroundComplement activation, regulation, and molecular basis for complement‐related diseases
Bajic, G., Degn, S. E., Thiel, S., & Andersen, G. R. (2015) · The EMBO Journal · doi:10.15252/embj.201591881 · Cited by 386
“In contrast, the polymorphism Y402H markedly reduced the ability of FH to bind MDA, indicating a causal link to disease etiology (Weismann et al , 2011).”
Risk factors and biomarkers of age-related macular degeneration
Lambert, N. G., Elshelmani, H., Singh, M. K., Mansergh, F. C., Wride, M. A., Padilla, M., Keegan, D., Hogg, R. E., & Ambati, B. K. (2016) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2016.04.003 · Cited by 367
“Increased levels of MDA provide one probable mechanism responsible for RPE cell death (Klein et al., 2013; Weismann et al., 2011).”
Atypical Hemolytic Uremic Syndrome
Kavanagh, D., Goodship, T. H. J., & Richards, A. (2013) · Seminars in Nephrology · doi:10.1016/j.semnephrol.2013.08.003 · Cited by 350
A guide to complement biology, pathology and therapeutic opportunity
Mastellos, D. C., Hajishengallis, G., & Lambris, J. D. (2023) · Nature reviews. Immunology · doi:10.1038/s41577-023-00926-1 · Cited by 351
“While the relative contribution of systemic complement stores versus local complement biosynthesis in the retina is still greatly debated, there is evidence for the contribution of both local and systemic mediators to AMD pathogenesis 199 , likely fuelled by an impaired blood–retina barrier allowing for ‘leakage’ of s…”
InfluentialOphthalmic drug discovery: novel targets and mechanisms for retinal diseases and glaucoma
Zhang, K., Zhang, L., & Weinreb, R. N. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3745 · Cited by 320
Riboflavin as a photosensitizer. Effects on human health and food quality
Cardoso, D. R., Libardi, S. H., & Skibsted, L. H. (2012) · Food & Function · doi:10.1039/c2fo10246c · Cited by 332
ApoE attenuates unresolvable inflammation by complex formation with activated C1q
Yin, C., Ackermann, S., Ma, Z., Mohanta, S. K., Zhang, C., Li, Y., Nietzsche, S., Westermann, M., Peng, L., Hu, D., et al. (2019) · Nature Medicine · doi:10.1038/s41591-018-0336-8 · Cited by 305
Self-citationB Cells and Humoral Immunity in Atherosclerosis
Tsiantoulas, D., Diehl, C. J., Witztum, J. L., & Binder, C. J. (2014) · Circulation Research · doi:10.1161/circresaha.113.301145 · Cited by 297
Sethi, S. M., Fervenza, F. C., Zhang, Y., Zand, L., Vrana, J. A., Nasr, S. H., Theis, J. D., Doǧan, A., & Smith, R. J. (2012) · Kidney International · doi:10.1038/ki.2012.212 · Cited by 297
“These polymorphisms lead to increased baseline AP activity even in normal controls, and studies comparing the H402 and Y402 variants of Factor H have shown that the former is associated with poorer AP control secondary to decreased binding to both endothelial cells and lipid peroxidation products like malondialdehyde,…”
ResultRPE necroptosis in response to oxidative stress and in AMD
Hanus, J., Anderson, C. A., & Wang, S. (2015) · Ageing Research Reviews · doi:10.1016/j.arr.2015.09.002 · Cited by 293
Handa, J. T., Rickman, C. B., Dick, A. D., Gorin, M. B., Miller, J. W., Toth, C. A., Ueffing, M., Zarbin, M. A., & Farrer, L. A. (2019) · Nature Communications · doi:10.1038/s41467-019-11262-1 · Cited by 285
Cholesterol in the retina: The best is yet to come
Pikuleva, I. A., & Curcio, C. A. (2014) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2014.03.002 · Cited by 287
Dry Age-Related Macular Degeneration: Mechanisms, Therapeutic Targets, and Imaging
Rickman, C. B., Farsiu, S., Toth, C. A., & Klingeborn, M. (2013) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.13-12757 · Cited by 293
“Recently, a study has shown that CFH may neutralize the pro-inflammatory effects of malondialdehyde (MDA)-induced inflammation in an AMD-risk associated manner.(82) This study suggests that CFH also functions to attenuate oxidative stress insults leading to AMD, which may explain why clinical trials using complement i…”
BackgroundThe Influence of Innate and Adaptive Immune Responses on Atherosclerosis
Witztum, J. L., & Lichtman, A. H. (2013) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-020712-163936 · Cited by 282
“CFH is the major plasma protein that binds MDA-modified protein (36).”
BackgroundInfluentialComplement factor H related proteins (CFHRs)
Skerka, C., Chen, Q., Frémeaux‐Bacchi, V., & Roumenina, L. T. (2013) · Molecular Immunology · doi:10.1016/j.molimm.2013.06.001 · Cited by 266
“and toperoxidized lipids ondead cells combinedwith reducedantiinflammatory functions by factor H (Weismann et al., 2011).”
BackgroundWilleit, P., Skroblin, P., Moschen, A. R., Yin, X., Kaudewitz, D., Zampetaki, A., Barwari, T., Whitehead, M., Ramírez, C. M., Goedeke, L., et al. (2016) · Diabetes · doi:10.2337/db16-0731 · Cited by 257
“Moreover, our comprehensive assessment of plasma proteins returned a positive correlation with afamin, which was previously linked to prevalent and new-onset metabolic syndrome and all its components (34), a positive correlation with complement factor H, a protein that binds malondialdehyde epitopes and protects from…”
BackgroundComplement activation by heme as a secondary hit for atypical hemolytic uremic syndrome
Frimat, M., Tabarin, F., Dimitrov, J. D., Poitou, C., Halbwachs‐Mecarelli, L., Frémeaux‐Bacchi, V., & Roumenina, L. T. (2013) · Blood · doi:10.1182/blood-2013-03-489245 · Cited by 250
Determinants of binding of oxidized phospholipids on apolipoprotein (a) and lipoprotein (a)
Leibundgut, G., Scipione, C. A., Yin, H., Schneider, M., Boffa, M. B., Green, S., Yang, X., Dennis, E. A., Witztum, J. L., Koschinsky, M. L., et al. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m040733 · Cited by 246
Ferrington, D. A., Sinha, D., & Kaarniranta, K. (2016) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2015.09.002 · Cited by 241
“It can potentiate drusen formation by inhibiting phagocytosis by macrophages and microglia to clear cellular debris present between RPE cells and Bruchs’membrane (Donoso et al., 2006, Buschini et al., 2011; Weismann et al., 2011).”
BackgroundThe Membrane Attack Complex in Aging Human Choriocapillaris
Mullins, R. F., Schoo, D. P., Sohn, E. H., Flamme‐Wiese, M. J., Workamelahu, G., Johnston, R. M., Wang, K., Tucker, B. A., & Stone, E. M. (2014) · American Journal Of Pathology · doi:10.1016/j.ajpath.2014.07.017 · Cited by 236
“In addition, the 402H form of CFH has a reduced affinity for Bruch’s membrane malondialdehyde.(46) Moreover, eyes homozygous for the Y402H polymorphism have increased deposition of MAC.”
BackgroundWhitmore, S. S., Sohn, E. H., Chirco, K. R., Drack, A. V., Stone, E. M., Tucker, B. A., & Mullins, R. F. (2014) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2014.11.005 · Cited by 223
“The Y402H allele reduces the ability of CFH to bind malondialdehyde adducts, potentially reducing the clearance of apoptotic cells (Weismann et al., 2011).”
BackgroundTsimikas, S., Willeit, P., Willeit, J., Santer, P., Mayr, M., Xu, Q., Mayr, A., Witztum, J. L., & Kiechl, S. J. (2012) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2012.08.979 · Cited by 219
“Recently, we demonstrated that complement factor H CFH), which is a primary regulator of the alternative athway of complement activation, strongly binds to MDA pitopes (24).”
Ceria‐Based Therapeutic Antioxidants for Biomedical Applications
Kim, Y. G., Lee, Y., Lee, N., Soh, M., Kim, D., & Hyeon, T. (2023) · Advanced Materials · doi:10.1002/adma.202210819 · Cited by 219
Protection of host cells by complement regulators
Schmidt, C. Q., Lambris, J. D., & Ricklin, D. (2016) · Immunological Reviews · doi:10.1111/imr.12475 · Cited by 208
Nrf2 signaling is impaired in the aging RPE given an oxidative insult
Sachdeva, M. M., Cano, M., & Handa, J. T. (2014) · Experimental Eye Research · doi:10.1016/j.exer.2013.10.024 · Cited by 207
“To establish whether these levels of superoxide anion were associated with oxidative damage to the RPE, we performed immunolabeling for malondialdehyde (MDA), a known lipid peroxidation product that has been identified in AMD (Weismann et al., 2011).”
On phagocytes and macular degeneration
Guillonneau, X., Eandi, C. M., Paques, M., Sahel, J.-A., Sapieha, P., & Sennlaub, F. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2017.06.002 · Cited by 185
“…rather as an additional trait of CFH402H, adding to its previously described decreased capacity to (i) inhibit oxidative stress (Shaw et al., 2012; Weismann et al., 2011), and (ii) to bind to Bruchs membrane (Clark et al., 2010), which might protect the RPE against uncontrolled complement…”
BackgroundInfluentialComplement factor H in host defense and immune evasion
Parente, R., Clark, S. J., Inforzato, A., & Day, A. J. (2016) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2418-4 · Cited by 199
“2), where the Y402H polymorphism leads to substantially impaired binding [123].”
BackgroundImmune mechanisms in inflammatory and degenerative eye disease
Perez, V. L., & Caspi, R. R. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.04.003 · Cited by 192
Complement Factor H Inhibits CD47-Mediated Resolution of Inflammation
Calippe, B., Augustin, S., Beguier, F., Charles-Messance, H., Poupel, L., Conart, J.-B., Hu, S. J., Lavalette, S., Fauvet, A., Rayes, J., et al. (2017) · Immunity · doi:10.1016/j.immuni.2017.01.006 · Cited by 168
The innate immune response to products of phospholipid peroxidation
Weismann, D., & Binder, C. J. (2012) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2012.01.018 · Cited by 174
The Relevance of Oxidative Stress in the Pathogenesis and Therapy of Retinal Dystrophies
Domènech, E. B., & Marfany, G. (2020) · Antioxidants · doi:10.3390/antiox9040347 · Cited by 175
“The major genetic risk factor to develop AMD is the Y402H polymorphism of complement factor H (CFH), which reduces CFH’s ability to neutralize the effect of oxidized photoreceptor phospholipids from photoreceptors, which are incorporated into the RPE membrane and trigger RPE cell apoptosis [83,84].”
Backgroundvan Dijk, R. A., Kolodgie, F. D., Ravandi, A., Leibundgut, G., Hu, P., Prasad, A., Mahmud, E., Dennis, E. A., Curtiss, L. K., Witztum, J. L., et al. (2012) · Journal of Lipid Research · doi:10.1194/jlr.p030890 · Cited by 169
Abokyi, S., To, C. H., Lam, T. T., & Tse, D. Y. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/7901270 · Cited by 180
“In the Y402H polymorphism, there is a marked reduction in the ability of the complement regulator CFH to bind to MDA, a lipid peroxidation product [154], leading to uncontrolled MDA-induced inflammation.”
BackgroundInfluentialAgrón, E., Mares, J. A., Clemons, T. E., Swaroop, A., Chew, E. Y., & Keenan, T. D. L. (2020) · Ophthalmology · doi:10.1016/j.ophtha.2020.08.018 · Cited by 173
Zhu, L., Zhai, Y., Wang, F., Hou, P., Lv, J., Xu, D., Shi, S., Liu, L., Yu, F., Zhao, M., et al. (2014) · Journal of the American Society of Nephrology · doi:10.1681/asn.2014010096 · Cited by 166
Oxidative stress, innate immunity, and age-related macular degeneration
Shaw, P. X., Stiles, T. L., Douglas, C. R., Ho, D., Fan, W., Du, H., & Xu, X. (2016) · AIMS molecular science · doi:10.3934/molsci.2016.2.196 · Cited by 175
“Wild-type CFH demonstrates a substantially increased affinity for oxidatively modified lipids such as oxPLs and malondialdehyde (MDA) compared to native, un-oxidized lipids [8,115,116].”
BackgroundThe complotype: dictating risk for inflammation and infection
Harris, C. L., Heurich, M., de Córdoba, S. R., & Morgan, B. P. (2012) · Trends in Immunology · doi:10.1016/j.it.2012.06.001 · Cited by 166
Complement factor H in AMD: Bridging genetic associations and pathobiology
Toomey, C. B., Johnson, L. V., & Rickman, C. B. (2017) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2017.09.001 · Cited by 162
“Using an unbiased proteomic approach to identify plasma proteins that interact with malondialdehyde (MDA), a marker of lipid peroxidation associated with oxidative stress, Weismann et al. discovered that CFH is a major MDA-binding protein and established it as an innate defense protein against MDA (Weismann et al., 20…”
BackgroundInfluentialHow does the macula protect itself from oxidative stress?
Handa, J. T. (2012) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.03.006 · Cited by 154
“Recently, in a multi-laboratory collaboration, we discovered that CFH, traditionally considered a major regulator of the alternative complement pathway, is a novel PRR that specifically recognizes MDA (Weismann et al., 2011).”
BackgroundImplications for reactive oxygen species in schizophrenia pathogenesis
Koga, M., Serritella, A. V., Sawa, A., & Sedlak, T. W. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2015.06.022 · Cited by 164
“Complement factor H appears to bind the lipid oxidation product, malonaldehyde, where it can attenuate further oxidative stress (Weismann et al., 2011).”
BackgroundOxidative stress and hepatitis C virus
Paracha, U. Z., Fatima, K., Alqahtani, M. H., Chaudhary, A., Abuzenadah, A. M., Damanhouri, G. A., & Qadri, I. (2013) · Virology Journal · doi:10.1186/1743-422x-10-251 · Cited by 161
Factor H: A Complement Regulator in Health and Disease, and a Mediator of Cellular Interactions
Kopp, A., Hebecker, M., Svobodová, E., & Józsi, M. (2012) · Biomolecules · doi:10.3390/biom2010046 · Cited by 160
“Malondialdehyde SCRs 7, 20 Protection from oxidative stress [50]”
BackgroundRegulation of age-related macular degeneration-like pathology by complement factor H
Toomey, C. B., Kelly, U., Saban, D. R., & Rickman, C. B. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1424391112 · Cited by 157
“A recent study uncovered a function for CFH in blocking the damaging effects of the lipid peroxidation product, malondialdehyde (72).”
BackgroundLipid Peroxidation in Atherosclerotic Cardiovascular Diseases
Gianazza, E., Brioschi, M., Fernandez, A. M., Casalnuovo, F., Altomare, A., Aldini, G., & Banfi, C. (2020) · Antioxidants and Redox Signaling · doi:10.1089/ars.2019.7955 · Cited by 164
“The MDA forms stable adducts with the major cellular biomolecules in different tissues and body fluids, such as lipids, proteins, free amino acids, and nucleotides, resulting in the loss of their structure and function and leading to alteration in cellular responses (281, 363, 401).”
Shaw, P. X., Zhang, L., Zhang, M., Du, H., Zhao, L., Lee, C., Grob, S., Lim, S. L., Hughes, G., Lee, J., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1121309109 · Cited by 148
“Recently, Weismann and coworkers (29) reported a link between CFH and oxidative stress in AMD.”
BackgroundClark, S. J., Ridge, L. A., Herbert, A. P., Hakobyan, S., Mulloy, B., Lennon, R., Würzner, R., Morgan, B. P., Uhrín, D., Bishop, P. N., et al. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1201751 · Cited by 152
“Another recent study has shown that a major CFH ligand is malondialdehyde (MDA), a common lipid peroxidation product found to accumulate in diseases such as AMD as a result of oxidative stress (46); for example, MDA is found on the surface of apoptotic/necrotic cells and blebs derived from these.”
InfluentialFactor H-related proteins determine complement-activating surfaces
Józsi, M., Tortajada, A., Uzonyi, B., de Jorge, E. G., & de Córdoba, S. R. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.04.008 · Cited by 149
Hajrasouliha, A. R., Jiang, G., Lu, Q., Lü, H., Kaplan, H. J., Zhang, H., & Shao, H. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.470765 · Cited by 147
Systemic and ocular fluid compounds as potential biomarkers in age-related macular degeneration
Kersten, E., Paun, C. C., Schellevis, R. L., Hoyng, C. B., Delcourt, C., Lengyel, I., Pető, T., Ueffing, M., Klaver, C. C. W., Dammeier, S., et al. (2017) · Survey of Ophthalmology · doi:10.1016/j.survophthal.2017.05.003 · Cited by 146
“Binding of MDA by IgM or macrophages leads to a proinflammatory response by increasing the expression of the inflammation factor interleukin (IL)-8,(274,358) whereas binding to FH attenuates inflammation.(358)”
BackgroundTisi, A., Feligioni, M., Passacantando, M., Ciancaglini, M., & Maccarone, R. (2021) · Cells · doi:10.3390/cells10010064 · Cited by 144
“ability to regulate the alternate complement pathway, the SCR7 domain is responsible for the CFH’s ability to bind lipid peroxidation products, such as malondialdehyde (MDA), released by the photoreceptors as a consequence of photo-oxidative stress [71].”
BackgroundContext-Dependent Role of Oxidized Lipids and Lipoproteins in Inflammation
Miller, Y. I., & Shyy, J. Y.-J. (2016) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2016.11.002 · Cited by 141
Oxidative Stress and Antioxidants in Age-Related Macular Degeneration
Kushwah, N. S., Bora, K., Maurya, M., Pavlovich, M. C., & Chen, J. (2023) · Antioxidants · doi:10.3390/antiox12071379 · Cited by 140
Regulation of regulators: Role of the complement factor H-related proteins
Cserhalmi, M., Papp, A., Brandus, B., Uzonyi, B., & Józsi, M. (2019) · Seminars in Immunology · doi:10.1016/j.smim.2019.101341 · Cited by 131
Sun, N., Chen, J., Wang, D., & Lin, S. (2018) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2018.08.010 · Cited by 132
Rational Engineering of a Minimized Immune Inhibitor with Unique Triple-Targeting Properties
Schmidt, C. Q., Bai, H., Lin, Z., Risitano, A. M., Barlow, P. N., Ricklin, D., & Lambris, J. D. (2013) · The Journal of Immunology · doi:10.4049/jimmunol.1203548 · Cited by 131
“The involvement of complement in the pathology of prevalent diseases such as age-related macular degeneration (AMD), together with its upstream role in controlling inflammatory processes, has fueled efforts to design complementtargeted therapeutics (5, 6).”
BackgroundMethodInfluentialAge-related macular degeneration and the role of the complement system
McHarg, S., Clark, S. J., Day, A. J., & Bishop, P. N. (2015) · Molecular Immunology · doi:10.1016/j.molimm.2015.02.032 · Cited by 131
Malondialdehyde epitopes as mediators of sterile inflammation
Busch, C. J., & Binder, C. J. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2016.06.016 · Cited by 127
Clark, S. J., Schmidt, C. Q., White, A. M., Hakobyan, S., Morgan, B. P., & Bishop, P. N. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1401613 · Cited by 122
“The unique FHL-1 C terminus means that it is necessary to investigate the binding characteristics of known FH ligands such as C-reactive protein (55, 56) and markers of oxidative stress (such as malondialdehyde) (57) in relationship to the Y402H polymorphism.”
BackgroundGenetic variants in the complement system predisposing to age-related macular degeneration: A review
Schramm, E. C., Clark, S. J., Triebwasser, M. P., Raychaudhuri, S., Seddon, J. M., & Atkinson, J. P. (2014) · Molecular Immunology · doi:10.1016/j.molimm.2014.06.032 · Cited by 122
“Furthermore, the Y402H polymorphism reduces the binding of FH to malondialdehyde (MDA), a peroxidation product that accumulates in AMD as a result of oxidative stress (Weismann et al., 2011).”
BackgroundInhibition of 12/15‐lipoxygenase as therapeutic strategy to treat stroke
Yiğitkanlı, K., Pekcec, A., Karataş, H., Pallast, S., Mandeville, E. T., Joshi, N., Smirnova, N., Gazaryan, I. G., Ratan, R. R., Witztum, J. L., et al. (2012) · Annals of Neurology · doi:10.1002/ana.23734 · Cited by 121
PyTMs: a useful PyMOL plugin for modeling common post-translational modifications
Warnecke, A., Sandalova, T., Achour, A., & Harris, R. A. (2014) · BMC Bioinformatics · doi:10.1186/s12859-014-0370-6 · Cited by 120
“There are accumulating examples of specific PTMs being recognized by scavenger receptors, complement components and antibodies due to alterations in structure and charge [12,15-17].”
Tsiantoulas, D., Perkmann, T., Afonyushkin, T., Mangold, A., Prohaska, T. A., Papac-Miličević, N., Millischer, V., Bartel, C., Hörkkö, S., Boulanger, C. M., et al. (2014) · Journal of Lipid Research · doi:10.1194/jlr.p054569 · Cited by 118
“(16, 34) To test whether MP induce chemokine expression via MDA-epitopes, we determined IL-8 secretion by THP-1 cells or primary human monocytes that were stimulated with platelet-derived MP in the presence of the MDA/MAA-specific IgM LR04 or an isotype control.”
Cruz‐Guilloty, F., Saeed, A. M., Echegaray, J. J., Duffort, S., Ballmick, A., Tan, Y., Betancourt, M., Viteri, E. J., Ramkhellawan, G. C., Ewald, E. J., et al. (2013) · International Journal of Inflammation · doi:10.1155/2013/503725 · Cited by 120
“For instance, it was recently demonstrated that complement factor H (CFH) serves a protective role in AMD by binding and inhibiting the inflammatory effects of the lipid peroxidation product malondialdehyde (MDA) [16] .”
BackgroundFunctional Anatomy of Complement Factor H
Makou, E., Herbert, A. P., & Barlow, P. N. (2013) · Biochemistry · doi:10.1021/bi4003452 · Cited by 120
Jun, S., Datta, S., Wang, L., Pegany, R. B., Cano, M., & Handa, J. T. (2018) · Experimental Eye Research · doi:10.1016/j.exer.2018.09.023 · Cited by 114
Lipids, oxidized lipids, oxidation-specific epitopes, and Age-related macular degeneration.
Handa, J. T., Cano, M., Wang, L., Datta, S., & Liu, T. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2016.07.013 · Cited by 112
Choroidal Neovascularization: Mechanisms of Endothelial Dysfunction
Yeo, N. J. Y., Chan, E. J. J., & Cheung, C. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.01363 · Cited by 120
Chen, J., Zeng, L., Xia, T., Li, S., Yan, T., Wu, S., Qiu, G., & Liu, Z. (2015) · Analytical Chemistry · doi:10.1021/acs.analchem.5b02032 · Cited by 113
Complement dysregulation and disease: From genes and proteins to diagnostics and drugs
de Córdoba, S. R., Tortajada, A., Harris, C. L., & Morgan, B. P. (2012) · Immunobiology · doi:10.1016/j.imbio.2012.07.021 · Cited by 113
Moss‐made pharmaceuticals: from bench to bedside
Ralf Reski, A., Parsons, J., & Decker, E. L. (2015) · Plant Biotechnology Journal · doi:10.1111/pbi.12401 · Cited by 110
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 112
“…of MDA epitopes identified so far are apoptotic/necrotic cells (Amir et al., 2012; Chang et al., 1999; Chang et al., 2004; Chou et al., 2009; Weismann et al., 2011), microvesicles (MV) (Huber et al., 2002; Liu, Scalia, Mehta, & Williams, 2012; Tsiantoulas et al., 2015) and oxidized…”
BackgroundMethodInfluentialYu, Y., Triebwasser, M. P., Wong, E. K. S., Schramm, E. C., Thomas, B., Reynolds, R. C., Mardis, E. R., Atkinson, J. P., Daly, M. J., Raychaudhuri, S., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu226 · Cited by 111
Gorin, M. B. (2012) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2012.04.004 · Cited by 105
“For example, Weissman et al (Weismann et al., 2011) has reported that the Y402H variant specifically affects the ability of complement factor H protein to bind malondialdehyde a common lipid peroxidation product that has been implicated in AMD.”
BackgroundLandowski, M., Kelly, U., Klingeborn, M., Groelle, M., Ding, J., Grigsby, D., & Rickman, C. B. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1814014116 · Cited by 104
“The Y402H polymorphism has been shown to decrease the binding of CFH to heparin (21, 25), M6 protein of Streptococcus pyogenes (25, 26), CRP (21, 25–27), Bruch’s membrane (BrM) (28), malondialdehyde (MDA) epitopes (29), and oxidized phospholipids (30).”
BackgroundKanner, J., Gorelik, S., Sirota, R., & Kohen, R. (2012) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf300193g · Cited by 103
Cipriani, V., Lorés‐Motta, L., He, F., Fathalla, D., Tilakaratna, V., McHarg, S., Bayatti, N., Acar, İ. E., Hoyng, C. B., Fauser, S., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-14499-3 · Cited by 104
Cano, M., Wang, L., Wan, J., Barnett, B. P., Ebrahimi, K. B., Qian, J. X., & Handa, J. T. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.01.004 · Cited by 102
Piccardi, M., Marangoni, D., Minnella, A. M., Savastano, M. C., Valentini, P., Ambrosio, L., Capoluongo, E., Maccarone, R., Bisti, S., & Falsini, B. (2012) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2012/429124 · Cited by 104
The Proteomics of DrusenPreprint
Crabb, J. W. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a017194 · Cited by 107
“Multiple lipoxidation products are present in drusen, Bruch’s membrane, and the cellular debris that copurifies with RPE lipofuscin granules (Crabb et al. 2002a; Gu et al. 2003a; Schutt et al. 2003; Shen et al. 2007; Ng et al. 2008; Weismann et al. 2011; Shaw et al. 2012).”
BackgroundInfluentialMicklisch, S., Lin, Y., Jacob, S., Karlstetter, M., Dannhausen, K., Dasari, P., von der Heide, M., Dahse, H., Schmölz, L., Graßmann, F., et al. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-016-0776-3 · Cited by 101
“Notably, in addition to surface complement activation, complement regulators like factor H and C4bp are recruited to the surfaces to restrict the complement cascade and to inhibit inflammation and autoimmune reactions [3, 21, 22].”
BackgroundNita, M., Grzybowski, A. E., Ascaso, F. J., & Huerva, V. (2014) · Mediators of Inflammation · doi:10.1155/2014/930671 · Cited by 128
“CFH binds to antigen epitopes, the part of an antigen recognized by antibodies, B cells, or T cells, and protects against oxidative stress [75].”
BackgroundSaccà, S. C., Roszkowska, A. M., & Izzotti, A. (2013) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2013.01.001 · Cited by 100
“These feature includes mutations in genes encoding for: (a) complement system factor 3 [302], and 5 [303]; the important role of complement factor H in protecting from oxidative stress and specifically from malondialdehyde products as occurring in AMD lesions have been demonstrated [304]; (b) HTRA1 secreted serine pro…”
BackgroundOxidation-Specific Biomarkers and Risk of Peripheral Artery Disease
Bertoia, M. L., Pai, J. K., Lee, J. H., Taleb, A., Joosten, M. M., Mittleman, M. A., Yang, X., Witztum, J. L., Rimm, E. B., Tsimikas, S., et al. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.02.047 · Cited by 97
“In response to uch danger-associated molecular patterns, macrophage cavenger receptors, immune effector proteins such as autontibodies to malondialdehyde-modified low-density liporotein (MDA-LDL), complement factor H (12), and -reactive protein have been selected and expanded to bind nd neutralize their pro-inflammato…”
Kenney, M. C., Chwa, M., Atilano, S. R., Pavlis, J. M., Falatoonzadeh, P., Ramírez, C., Malik, D., Hsu, T., Woo, G., Soe, K., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054339 · Cited by 97
“The CFH protein with the high risk Tyr402His polymorphism has a reduced capacity to bind with malondialdehyde (MDA), a lipid peroxidation cytotoxin, which could possibly contribute to a defective innate immune response for AMD patients [47].”
BackgroundMalaria Parasites Co-opt Human Factor H to Prevent Complement-Mediated Lysis in the Mosquito Midgut
Simon, N., Lasonder, E., Scheuermayer, M., Kuehn, A., Tews, S., Fischer, R., Zipfel, P. F., Skerka, C., & Pradel, G. (2013) · Cell Host & Microbe · doi:10.1016/j.chom.2012.11.013 · Cited by 94
“For the latter two C3b-binding sites and for module CCP7 heparin binding was described (Kühn et al., 1995; Blackmore et al., 1998; Prodinger et al., 1998; Weismann et al., 2011).”
Background
Metadata
- Authors
- Weismann, D., Hartvigsen, K., Lauer, N., Bennett, K. L., Scholl, H. P. N., Issa, P. C., Cano, M., Brandstätter, H., Tsimikas, S., Skerka, C., Superti-Furga, G., Handa, J. T., Zipfel, P. F., Witztum, J. L., & Binder, C. J.
- Affiliations
- Austrian Academy of Sciences (AT)
- Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
- Johns Hopkins University (US)
- University of Oxford (GB)
- Octapharma (Austria) (AT)
- University of California San Diego (US)
- Corresponding author
- Binder, Christoph J.
- ORCID
- Venue
- Nature
- Published
- 2011-10
- Volume
- 478
- Issue
- 7367
- Pages
- 76-81
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4826616
- OpenAlex
- W2062097745
- Cited by
- 533
- References
- 42
- Citations by year
- 2026: 16 · 2025: 24 · 2024: 25 · 2023: 30 · 2022: 29 · 2021: 42 · 2020: 36 · 2019: 29 · 2018: 33 · 2017: 31 · 2016: 39 · 2015: 42 · 2014: 44 · 2013: 66 · 2012: 44
- FWCI
- 22.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01-HL086599, HL-088093, P01HL088093)
- National Eye Institute (EY14005, R01EY014005, EY019044, R01EY019904)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Complement system in diseases
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
- Keywords
- complement factor H, malondialdehyde, lipid peroxidation, oxidative stress, age-related macular degeneration, macrophage uptake, pro-inflammatory effects, innate immunity, chronic inflammation, retina
- MeSH terms
- Animals, Epitopes, Binding Sites, Complement System Proteins, Complement Inactivator Proteins, Enzyme-Linked Immunosorbent Assay, Female, Humans, Inflammation, Macular Degeneration, Male, Malondialdehyde, Mice, Inbred C57BL, Mutation, Necrosis, Protein Binding, Retina, Lipid Peroxidation, Apoptosis, Complement Factor H, Protein Structure, Tertiary, Macrophages, Peritoneal, Oxidative Stress, Mice
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