Direct evidence of a role for Nox2 in superoxide production, reduced nitric oxide bioavailability, and early atherosclerotic plaque formation in ApoE−/−mice
Abstract
The Nox family NADPH oxidases are reactive oxygen species (ROS)-generating enzymes that are strongly implicated in atherogenesis. However, no studies have examined which Nox isoform(s) are involved. Here we investigated the role of the Nox2-containing NADPH oxidase in atherogenesis in apolipoprotein E-null (ApoE−/−) mice. Wild-type (C57Bl6/J), ApoE−/−, and Nox2−/y/ApoE−/−mice were maintained on a high-fat (21%) diet from 5 wk of age until they were 12 or 19 wk old. Mice were euthanized and their aortas removed for measurement of Nox2 expression (Western blot analysis and immunohistochemistry), ROS production (L012-enhanced chemiluminescence), nitric oxide (NO) bioavailability (contractions to N ω-nitro-l-arginine), and atherosclerotic plaque development along the aorta and in the aortic sinus. Nox2 expression was upregulated in the aortic endothelium of ApoE−/−mice before the appearance of lesions, and this was associated with elevated ROS levels. Within developing plaques, macrophages were also a prominent source of Nox2. The absence of Nox2 in Nox2−/y/ApoE−/−double-knockout mice had minimal effects on plasma lipids or lesion development in the aortic sinus in animals up to 19 wk of age. However, an en face examination of the aorta from the arch to the iliac bifurcation revealed a 50% reduction in lesion area in Nox2−/y/ApoE−/−versus ApoE−/−mice, and this was associated with a marked decrease in aortic ROS production and an increased NO bioavailability. In conclusion, this is the first demonstration of a role for Nox2-NADPH oxidase in vascular ROS production, reduced NO bioavailability, and early lesion development in ApoE−/−mice, highlighting this Nox isoform as a potential target for future therapies for atherosclerosis.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The combination of NOX2−/− with ApoE−/− can decrease atherosclerotic lesions, but this is not always the case.
“The combination of NOX2−/− with ApoE−/− can decrease the atherosclerotic lesions (475), but this is not always the case (508).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [475]
Cites
The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology
Bedard, K., & Krause, K.-H. (2007) · Physiological Reviews · doi:10.1152/physrev.00044.2005 · Cited by 6,989 · see citing works
Endothelial Nitric Oxide Synthase in Vascular Disease: From Marvel to Menace
Förstermann, U., & Münzel, T. (2006) · Circulation · doi:10.1161/circulationaha.105.602532 · Cited by 1,957 · cited 1× · see citing works
“, oxygen reduction is uncoupled from L-arginine oxidation such that it switches from an antiatherogenic NO-producing enzyme to one that generates superoxide, thereby itself becoming a contributor to vascular oxidative stress (13).”
BackgroundPollock, J. D., Williams, D. A., Gifford, M. A. C., Li, L. L., Du, X., Fisherman, J., Orkin, S. H., Doerschuk, C. M., & Dinauer, M. C. (1995) · Nature Genetics · doi:10.1038/ng0295-202 · Cited by 921 · see citing works
Superoxide Production and Expression of Nox Family Proteins in Human Atherosclerosis
Sorescu, D., Weiss, D., Lassègue, B., Clempus, R. E., Szöcs, K., Sorescu, G. P., Valppu, L., Quinn, M. T., Lambeth, J. D., Vega, J. D., et al. (2002) · Circulation · doi:10.1161/01.cir.0000012917.74432.66 · Cited by 847 · see citing works
Functional analysis of Nox4 reveals unique characteristics compared to other NADPH oxidases
Martyn, K. D., Frederick, L. M., von Loehneysen, K., Dinauer, M. C., & Knaus, U. G. (2006) · Cellular Signalling · doi:10.1016/j.cellsig.2005.03.023 · Cited by 783 · see citing works
Laursen, J. B., Somers, M., Kurz, S., McCann, L., Warnholtz, A., Freeman, B. A., Tarpey, M., Fukai, T., & Harrison, D. G. (2001) · Circulation · doi:10.1161/01.cir.103.9.1282 · Cited by 721 · see citing works
Mollnau, H., Wendt, M., Szöcs, K., Lassègue, B., Schulz, E., Oelze, M., Li, H., Bodenschatz, M., August, M., Kleschyov, A. L., et al. (2002) · Circulation Research · doi:10.1161/01.res.0000012569.55432.02 · Cited by 676 · see citing works
Kuhlencordt, P. J., Gyurko, R., Han, F., Scherrer‐Crosbie, M., Aretz, T. H., Hajjar, R. J., Picard, M. H., & Huang, P. L. (2001) · Circulation · doi:10.1161/hc2901.091399 · Cited by 631 · see citing works
Ambasta, R. K., Kumar, P., Griendling, K. K., Schmidt, H. H. H. W., Busse, R., & Brandes, R. P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406486200 · Cited by 541 · see citing works
p47phox is required for atherosclerotic lesion progression in ApoE–/– mice
Barry-Lane, P. A., Patterson, C., van der Merwe, M., Hu, Z., Holland, S. M., Yeh, E. T. H., & Runge, M. S. (2001) · Journal of Clinical Investigation · doi:10.1172/jci200111927 · Cited by 489 · see citing works
Thomas, S. R., Witting, P. K., & Drummond, G. R. (2008) · Antioxidants & Redox Signaling · doi:10.1089/ars.2008.2027 · Cited by 383 · see citing works
Self-citationRegulation of Superoxide Anion Production by NADPH Oxidase in Monocytes/Macrophages
Cathcart, M. K. (2003) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000097769.47306.12 · Cited by 365 · see citing works
Redox Mechanisms in Blood Vessels
Mueller, C. F. H., Laude, K. M., McNally, J. S., & Harrison, D. G. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000149143.04821.eb · Cited by 342 · see citing works
Selemidis, S., Sobey, C. G., Wingler, K., Schmidt, H. H. H. W., & Drummond, G. R. (2008) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2008.08.005 · Cited by 241 · see citing works
Self-citationMeasurement of NAD(P)H oxidase-derived superoxide with the luminol analogue L-012
Daiber, A., August, M., Baldus, S. E., Wendt, M., Oelze, M. W., Sydow, K., Kleschyov, A. L., & Münzel, T. F. (2003) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2003.10.012 · Cited by 184 · see citing works
Vendrov, A. E., Hakim, Z. S., Madamanchi, N. R., Rojas, M., Madamanchi, C., & Runge, M. S. (2007) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.107.152629 · Cited by 173 · see citing works
Bleys, J., Miller, E. R., Pastor‐Barriuso, R., Appel, L. J., & Güallar, E. (2006) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/84.4.880 · Cited by 173 · see citing works
Kirk, E. A., Dinauer, M. C., Rosen, H., Chait, A., Heinecke, J. W., & LeBoeuf, R. C. (2000) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.20.6.1529 · Cited by 171 · see citing works
Hsich, E., Segal, B. H., Pagano, P. J., Rey, F. E., Paigen, B., Deleonardis, J., Hoyt, R. F., Holland, S. M., & Finkel, T. (2000) · Circulation · doi:10.1161/01.cir.101.11.1234 · Cited by 158 · see citing works
Novel isoforms of NADPH oxidase in vascular physiology and pathophysiology
BENGTSSON, S. H. M., Gulluyan, L. M., Dusting, G. J., & Drummond, G. R. (2003) · Clinical and Experimental Pharmacology and Physiology · doi:10.1046/j.1440-1681.2003.03929.x · Cited by 135 · see citing works
Self-citationDifferential effects of diabetes on the expression of the gp91phox homologues nox1 and nox4
Wendt, M. C., Daiber, A., Kleschyov, A. L., Mülsch, A., Sydow, K., Schulz, E., Chen, K., Keaney, J. F., Lassègue, B., Walter, U., et al. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.03.020 · Cited by 122 · see citing works
Rosenblat, M., & Aviram, M. (2002) · Atherosclerosis · doi:10.1016/s0021-9150(01)00563-9 · Cited by 100 · see citing works
Noxa1 is a central component of the smooth muscle NADPH oxidase in mice
Ambasta, R. K., Schreiber, J. G., Janiszewski, M., Busse, R., & Brandes, R. P. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.12.035 · Cited by 90 · see citing works
Silva, T. M. D., Broughton, B. R. S., Drummond, G. R., Sobey, C. G., & Miller, A. A. (2009) · Stroke · doi:10.1161/strokeaha.108.531707 · Cited by 83 · see citing works
Self-citationComposition and Functions of Vascular Nicotinamide Adenine Dinucleotide Phosphate Oxidases
Brandes, R. P., & Schröder, K. (2008) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2007.11.001 · Cited by 67 · see citing works
Björgvinsdóttir, H., Zhen, L., & Dinauer, M. (1996) · Blood · doi:10.1182/blood.v87.5.2005.2005 · Cited by 63 · see citing works
Opitz, N., Drummond, G. R., Selemidis, S., Meurer, S., & Schmidt, H. H. H. W. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.11.003 · Cited by 60 · see citing works
Self-citationPonnuswamy, P., Ostermeier, E., Schröttle, A., Chen, J., Huang, P. L., Ertl, G., Nieswandt, B., & Kuhlencordt, P. J. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.080730 · Cited by 60 · see citing works
Subcellular localization and function of alternatively spliced Noxo1 isoforms
Ueyama, T., Lekstrom, K. J., Tsujibe, S., Saito, N., & Leto, T. L. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.08.024 · Cited by 59 · see citing works
Bey, E. A., & Cathcart, M. K. (2000) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)34488-6 · Cited by 45 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Reactive Oxygen Species in Metabolic and Inflammatory Signaling
Forrester, S. J., Kikuchi, D. S., Hernandes, M. S., Xu, Q., & Griendling, K. K. (2018) · Circulation Research · doi:10.1161/circresaha.117.311401 · Cited by 2,081 · see citing works
Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis
Förstermann, U., Xia, N., & Li, H. (2017) · Circulation Research · doi:10.1161/circresaha.116.309326 · Cited by 1,519 · see citing works
Durham, A. L., Speer, M. Y., Scatena, M., Giachelli, C. M., & Shanahan, C. M. (2018) · Cardiovascular Research · doi:10.1093/cvr/cvy010 · Cited by 1,131 · see citing works
Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets
Drummond, G. R., Selemidis, S., Griendling, K. K., & Sobey, C. G. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3403 · Cited by 899 · see citing works
Self-citationOxidative Stress in Cardiovascular Diseases: Still a Therapeutic Target?
Senoner, T., & Dichtl, W. (2019) · Nutrients · doi:10.3390/nu11092090 · Cited by 880 · see citing works
Reactive oxygen species in cardiovascular disease
Sugamura, K., & Keaney (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.05.004 · Cited by 769 · see citing works
Biochemistry, Physiology, and Pathophysiology of NADPH Oxidases in the Cardiovascular System
Lassegue, B. P., Martín, A. S., & Griendling, K. K. (2012) · Circulation Research · doi:10.1161/circresaha.111.243972 · Cited by 768 · see citing works
Vascular oxidative stress, nitric oxide and atherosclerosis
Li, H., Horke, S., & Förstermann, U. (2014) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2014.09.001 · Cited by 656 · see citing works
NADPH Oxidases: Functions and Pathologies in the Vasculature
Lassègue, B., & Griendling, K. K. (2010) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.108.181610 · Cited by 592 · see citing works
Eelen, G., de Zeeuw, P., Treps, L., Harjes, U., Wong, B. W., & Carmeliet, P. (2017) · Physiological Reviews · doi:10.1152/physrev.00001.2017 · Cited by 591 · see citing works
The Role of Oxidative Stress in Atherosclerosis
Batty, M., Bennett, M. R., & Yu, E. (2022) · Cells · doi:10.3390/cells11233843 · Cited by 569 · see citing works
Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
Tejero, J., Shiva, S., & Gladwin, M. T. (2019) · Physiological Reviews · doi:10.1152/physrev.00036.2017 · Cited by 541 · see citing works
NADPH oxidases and oxidase crosstalk in cardiovascular diseases: novel therapeutic targets
Zhang, Y., Murugesan, P., Huang, K., & Cai, H. “. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-019-0260-8 · Cited by 546 · see citing works
Evolution of nadph oxidase inhibitors: Selectivity and mechanisms for target engagement
Altenhöfer, S., Radermacher, K. A., Kleikers, P. W. M., Wingler, K., & Schmidt, H. H. H. W. (2015) · Antioxidants & Redox Signaling · doi:10.1089/ars.2013.5814 · Cited by 521 · see citing works
Molecular Biology of Atherosclerosis
Hopkins, P. N. (2013) · Physiological Reviews · doi:10.1152/physrev.00004.2012 · Cited by 456 · see citing works
NLRP3 inflammasome: Its regulation and involvement in atherosclerosis
Hoseini, Z. S., Sepahvand, F., Rashidi, B., Sahebkar, A., Masoudifar, A., & Mirzaei, H. (2017) · Journal of Cellular Physiology · doi:10.1002/jcp.25930 · Cited by 458 · see citing works
NADPH Oxidases in Vascular Pathology
Konior, A., Schramm‐Luc, A., Cześnikiewicz‐Guzik, M., & Guzik, T. J. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5607 · Cited by 451 · see citing works
Oxidative Stress-Induced Endothelial Dysfunction in Cardiovascular Diseases
Shaito, A. A., Aramouni, K., Assaf, R., Parenti, A., Orekhov, A. N., EL‐Yazbi, A. F., Pintus, G., & Eid, A. H. (2022) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2703105 · Cited by 427 · see citing works
NADPH Oxidase 1 Plays a Key Role in Diabetes Mellitus–Accelerated Atherosclerosis
Gray, S. P., Di Marco, E., Okabe, J., Szyndralewiez, C., Heitz, F., Montezano, A. C., de Haan, J. B., Koulis, C., El-Osta, A., Andrews, K. L., et al. (2013) · Circulation · doi:10.1161/circulationaha.112.132159 · Cited by 386 · see citing works
Anti-inflammatory therapies for atherosclerosis
Bäck, M., & Hansson, G. K. (2015) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2015.5 · Cited by 380 · see citing works
Redox control of inflammation in macrophages
Brüne, B., Dehne, N., Grossmann, N., Jung, M., Namgaladze, D., Schmid, T., von Knethen, A., & Weigert, A. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4785 · Cited by 377 · see citing works
The Renin-Angiotensin-Aldosterone System in Vascular Inflammation and Remodeling
Pacurari, M., Kafoury, R., Tchounwou, P. B., & Ndebele, K. (2014) · International Journal of Inflammation · doi:10.1155/2014/689360 · Cited by 377 · see citing works
Endothelial NADPH oxidases: which NOX to target in vascular disease?
Drummond, G. R., & Sobey, C. G. (2014) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2014.06.012 · Cited by 315 · see citing works
Self-citationCervantes-Gracia, K., Llanas-Cornejo, D., & Husi, H. (2017) · Journal of Clinical Medicine · doi:10.3390/jcm6020022 · Cited by 314 · see citing works
Li, G., Scull, C. M., Özcan, L., & Tabas, I. A. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.201006121 · Cited by 306 · see citing works
Protective Effects of Estrogen on Cardiovascular Disease Mediated by Oxidative Stress
Xiang, D., Liu, Y., Zhou, S.-J., Zhou, E., & Wang, Y. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/5523516 · Cited by 262 · see citing works
Wang, Y., Wang, G. Z., Rabinovitch, P. S., & Tabas, I. A. (2013) · Circulation Research · doi:10.1161/circresaha.114.302153 · Cited by 264 · see citing works
NADPH oxidases in cardiovascular disease
Brandes, R. P., Weißmann, N., & Schröder, K. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.04.030 · Cited by 266 · see citing works
Kim, S. Y., Jeong, J., Kim, S. J., Seo, W., Kim, M., Choi, W., Yoo, W., Lee, J. H., Shim, Y., Yi, H., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-02325-2 · Cited by 258 · see citing works
Vascular Oxidative Stress: Impact and Therapeutic Approaches
Sena, C. M., Leandro, A., Azul, L., Seiça, R. M. F., & Perry, G. L. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01668 · Cited by 260 · see citing works
Redox Roles of Reactive Oxygen Species in Cardiovascular Diseases
He, F. J., & Zuo, L. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms161126059 · Cited by 240 · see citing works
Redox signaling in cardiovascular health and disease
Madamanchi, N. R., & Runge, M. S. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.04.001 · Cited by 223 · see citing works
Vendrov, A. E., Vendrov, K. C., Smith, A., Yuan, J., Sumida, A., Robidoux, J., Runge, M. S., & Madamanchi, N. R. (2015) · Antioxidants and Redox Signaling · doi:10.1089/ars.2014.6221 · Cited by 219 · see citing works
Oxidative stress and cardiovascular disease: new insights
Pignatelli, P., Menichelli, D., Pastori, D., & Violi, F. (2018) · Kardiologia Polska · doi:10.5603/kp.a2018.0071 · Cited by 212 · see citing works
Discovery of GSK2795039, a Novel Small Molecule NADPH Oxidase 2 Inhibitor
Hirano, K., Chen, W. S., Chueng, A. L. W., Dunne, A. A., Seredenina, T., Filippova, A., Ramachandran, S., Bridges, A., Chaudry, L., Pettman, G., et al. (2015) · Antioxidants & Redox Signaling · doi:10.1089/ars.2014.6202 · Cited by 205 · see citing works
Gray, S. P., Di Marco, E., Kennedy, K., Chew, P., Okabe, J., El-Osta, A., Calkin, A. C., Biessen, E. A. L., Touyz, R. M., Cooper, M. E., et al. (2016) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.115.307012 · Cited by 189 · see citing works
NADPH Oxidases: From Molecular Mechanisms to Current Inhibitors
Cipriano, A., Viviano, M., Feoli, A., Milite, C., Sarno, G., Castellano, S., & Sbardella, G. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c00770 · Cited by 190 · see citing works
NADPH oxidases in cardiovascular disease: insights from in vivo models and clinical studies
Sirker, A. A., Zhang, M., & Shah, A. M. (2011) · Basic Research in Cardiology · doi:10.1007/s00395-011-0190-z · Cited by 180 · see citing works
The NADPH oxidase Nox4 has anti-atherosclerotic functions
Schürmann, C., Rezende, F., Kruse, C., Yasar, Y., Löwe, O., Fork, C., van de Sluis, B., Bremer, R., Weißmann, N., Shah, A. M., et al. (2015) · European Heart Journal · doi:10.1093/eurheartj/ehv460 · Cited by 178 · see citing works
From form to function: the role of Nox4 in the cardiovascular system
Chen, F., Haigh, S. B., Barman, S. A., & Fulton, D. J. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00412 · Cited by 172 · see citing works
Rac1 in human diseases: The therapeutic potential of targeting Rac1 signaling regulatory mechanisms
Marei, H., & Malliri, A. (2016) · Small GTPases · doi:10.1080/21541248.2016.1211398 · Cited by 168 · see citing works
Byon, C. H., Heath, J. M., & Chen, Y. (2016) · Redox Biology · doi:10.1016/j.redox.2016.08.015 · Cited by 164 · see citing works
Recent novel approaches to limit oxidative stress and inflammation in diabetic complications
Pickering, R. J., Rosado, C. J., Sharma, A., Buksh, S., Tate, M., & de Haan, J. B. (2018) · Clinical & Translational Immunology · doi:10.1002/cti2.1016 · Cited by 164 · see citing works
Dysfunction of Cerebrovascular Endothelial Cells: Prelude to Vascular Dementia
Wang, F., Cao, Y., Ma, L., Pei, H., Rausch, W., & Li, H. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00376 · Cited by 160 · see citing works
Park, L., Wang, G., Zhou, P., Zhou, J., Pitstick, R., Previti, M. L., Younkin, L., Younkin, S. G., Van Nostrand, W. E., Cho, S., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1015413108 · Cited by 156 · see citing works
Endosomal nox2 oxidase exacerbates virus pathogenicity and is a target for antiviral therapy
To, E. E., Vlahos, R., Luong, R., Halls, M. L., Reading, P. C., King, P. T., Chan, C., Drummond, G. R., Sobey, C. G., Broughton, B. R. S., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00057-x · Cited by 154 · see citing works
Self-citationLipid 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 158 · see citing works
Yin, K., Liao, D., & Tang, C. (2010) · Molecular Medicine · doi:10.2119/molmed.2010.00004 · Cited by 152 · see citing works
Role for Nox1 NADPH oxidase in atherosclerosis
Sheehan, A. L., Carrell, S., Johnson, B., Stanić, B., Bánfi, B., & Miller, F. J. (2011) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2011.02.028 · Cited by 148 · see citing works
The Role of Oxidative Stress and Autophagy in Atherosclerosis
Perrotta, I. D., & Aquila, S. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/130315 · Cited by 147 · see citing works
NADPH oxidases: key modulators in aging and age-related cardiovascular diseases?
Sahoo, S., Meijles, D. N., & Pagano, P. J. (2016) · Clinical Science · doi:10.1042/cs20150087 · Cited by 146 · see citing works
The Nox Family of NADPH Oxidases: Friend or Foe of the Vascular System?
Takac, I., Schröder, K., & Brandes, R. P. (2011) · Current Hypertension Reports · doi:10.1007/s11906-011-0238-3 · Cited by 142 · see citing works
Role of Vascular Oxidative Stress in Obesity and Metabolic Syndrome
Youn, J.-Y., Siu, K. L., Lob, H. E., Itani, H. A., Harrison, D. G., & Cai, H. “. (2014) · Diabetes · doi:10.2337/db13-0719 · Cited by 138 · see citing works
NADPH oxidases and vascular remodeling in cardiovascular diseases
García‐Redondo, A. B., Aguado, A., Briones, A. M., & Salaíces, M. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.10.015 · Cited by 137 · see citing works
Langbein, H., Brunssen, C., Hofmann, A., Cimalla, P., Brux, M., Bornstein, S. R., Deussen, A., Koch, E., & Morawietz, H. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehv564 · Cited by 133 · see citing works
Fan, L. M., Douglas, G., Bendall, J. K., McNeill, E., Crabtree, M. J., Hale, A., Mai, A., Li, J., McAteer, M. A., Schneider, J. E., et al. (2014) · Circulation · doi:10.1161/circulationaha.113.005062 · Cited by 134 · see citing works
Oxidative Stress in Cardiovascular Diseases and Obesity: Role of p66Shc and Protein Kinase C
Marchi, E. D., Baldassari, F., Bononi, A., Wieckowski, M. R., & Pinton, P. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/564961 · Cited by 132 · see citing works
Oxidative Stress in Cell Death and Cardiovascular Diseases
Xu, T., Ding, W., Ji, X., Ao, X., Liu, Y., Yu, W., & Wang, J. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/9030563 · Cited by 131 · see citing works
The NADPH Oxidase Family and its Inhibitors
Kleniewska, P., Piechota-Polańczyk, A., Skibska, B., & Gorąca, A. (2012) · Archivum Immunologiae et Therapiae Experimentalis · doi:10.1007/s00005-012-0176-z · Cited by 126 · see citing works
Oxidative Stress in Cardiovascular Disease
Csányi, G., & Jr., F. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15046002 · Cited by 130 · see citing works
Zielonka, J., Lambeth, J. D., & Kalyanaraman, B. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.09.017 · Cited by 128 · see citing works
Redox regulation of the actin cytoskeleton and its role in the vascular system
Xu, Q., Huff, L. P., Fujii, M., & Griendling, K. K. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2017.03.004 · Cited by 129 · see citing works
Actions of “antioxidants” in the protection against atherosclerosis
Lönn, M. E., Dennis, J. M., & Stocker, R. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.05.027 · Cited by 124 · see citing works
Nitric oxide and mitochondria in metabolic syndrome
Litvinova, L. S., Atochin, D. N., Fattakhov, N. S., Василенко, М., Затолокин, П. А., & Кириенкова, Е. В. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00020 · Cited by 127 · see citing works
Leo, C., Hart, J. L., & Woodman, O. L. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.01023.x · Cited by 122 · see citing works
Evolving Concepts of Oxidative Stress and Reactive Oxygen Species in Cardiovascular Disease
Chen, K., & Keaney, J. F. (2012) · Current Atherosclerosis Reports · doi:10.1007/s11883-012-0266-8 · Cited by 119 · see citing works
Atherothrombosis and Oxidative Stress: Mechanisms and Management in Elderly
Violi, F., Loffredo, L., Carnevale, R., Pignatelli, P., & Pastori, D. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2016.6963 · Cited by 121 · see citing works
Oxidative Stress, Nox Isoforms and Complications of Diabetes—Potential Targets for Novel Therapies
Sedeek, M. H., Montezano, A. C. I., Hébert, R., Gray, S. P., Marco, E. D., Jha, J. C., Cooper, M. E., Jandeleit-Dahm, K. A. M., Schiffrin, E. L., Wilkinson‐Berka, J. L., et al. (2012) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-012-9387-2 · Cited by 116 · see citing works
Regulation of NAD(P)H oxidases by AMPK in cardiovascular systems
Song, P., & Zou, M. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.01.025 · Cited by 119 · see citing works
Xiao, L., Liu, L., Guo, X., Zhang, S., Wang, J., Zhou, F., Liu, L., Tang, Y., & Yao, P. (2017) · Food and Chemical Toxicology · doi:10.1016/j.fct.2017.03.048 · Cited by 113 · see citing works
Douglas, G., Bendall, J. K., Crabtree, M. J., Tatham, A. L., Carter, E. E., Hale, A. B., & Channon, K. M. (2012) · Cardiovascular Research · doi:10.1093/cvr/cvs026 · Cited by 111 · see citing works
Role of oxidative stress in calcific aortic valve disease and its therapeutic implications
Greenberg, H. Z. E., Zhao, G., Shah, A. M., & Zhang, M. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab142 · Cited by 110 · see citing works
Hofmann Bowman, M. A., Gawdzik, J., Bukhari, U., Husain, A. N., Toth, P. T., Kim, G., Earley, J., & McNally, E. M. (2011) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.110.217745 · Cited by 111 · see citing works
Reuland, D. J., Khademi, S., Castle, C. J., Irwin, D. C., McCord, J. M., Miller, B. F., & Hamilton, K. L. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.11.016 · Cited by 110 · see citing works
Emerging role of PKA/eNOS pathway in therapeutic angiogenesis for ischaemic tissue diseases
Bir, S. C., Xiong, Y., Kevil, C. G., & Luo, J. (2012) · Cardiovascular Research · doi:10.1093/cvr/cvs143 · Cited by 107 · see citing works
ROS and RNS Signaling in Heart Disorders: Could Antioxidant Treatment Be Successful?
Afanasʹev, I. B. (2011) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2011/293769 · Cited by 106 · see citing works
Nox isoforms in vascular pathophysiology: insights from transgenic and knockout mouse models
Rivera, J., Sobey, C. G., Walduck, A. K., & Drummond, G. R. (2010) · Redox Report · doi:10.1179/174329210x12650506623401 · Cited by 105 · see citing works
Self-citationScott, T., Lewis, C., Zhu, M., Wang, C., Samuel, C. S., Drummond, G. R., & Kemp‐Harper, B. K. (2023) · Scientific Reports · doi:10.1038/s41598-023-46237-2 · Cited by 106 · see citing works
Self-citationNADPH oxidases: redox regulation of cell homeostasis and disease
Kračun, D., Lopes, L. R., Cifuentes-Pagano, E., & Pagano, P. J. (2025) · Physiological Reviews · doi:10.1152/physrev.00034.2023 · Cited by 104 · see citing works
Tiyerili, V., Zimmer, S., Jung, S., Wassmann, K., Naehle, C. P., Lütjohann, D., Zimmer, A., Nickenig, G., & Waßmann, S. (2010) · Basic Research in Cardiology · doi:10.1007/s00395-010-0090-7 · Cited by 99 · see citing works
Dihydromyricetin ameliorates atherosclerosis in LDL receptor deficient mice
Liu, T. T., Zeng, Y., Tang, K., Chen, X., Zhang, W., & Xu, X. L. (2017) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2017.05.003 · Cited by 100 · see citing works
NADPH Oxidase-2 and Atherothrombosis
Violi, F., Carnevale, R., Loffredo, L., Pignatelli, P., & Gallin, J. I. (2016) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.116.308351 · Cited by 99 · see citing works
NADPH Oxidases as Regulators of Tumor Angiogenesis: Current and Emerging Concepts
Coso, S., Harrison, I., Harrison, C. B., Vinh, A., Sobey, C. G., Drummond, G. R., Williams, E. D., & Selemidis, S. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4489 · Cited by 99 · see citing works
Self-citationRole of reactive oxygen species in atherosclerosis: Lessons from murine genetic models
Nègre‐Salvayre, A., Guerby, P., Gayral, S., Laffargue, M., & Salvayre, R. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2019.10.011 · Cited by 98 · see citing works
The opposing roles of NO and oxidative stress in cardiovascular disease
Ritchie, R. H., Drummond, G. R., Sobey, C. G., Silva, T. M. D., & Kemp‐Harper, B. K. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.12.017 · Cited by 98 · see citing works
Self-citationNOX2 As a Target for Drug Development: Indications, Possible Complications, and Progress
Diebold, B. A., Smith, S. M., Yang, L., & Lambeth, J. D. (2014) · Antioxidants and Redox Signaling · doi:10.1089/ars.2014.5862 · Cited by 96 · see citing works
Reactive Oxygen Species in Endothelial Function – From Disease to Adaptation –
Craige, S. M., Kant, S., & Keaney, J. F. (2015) · Circulation Journal · doi:10.1253/circj.cj-15-0464 · Cited by 91 · see citing works
Age-related diseases as vicious cycles
Belikov, A. V. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.11.002 · Cited by 92 · see citing works
Identification of a Non-Growth Factor Role for GM-CSF in Advanced Atherosclerosis
Subramanian, M., Thorp, E. B., & Tabas, I. A. (2014) · Circulation Research · doi:10.1161/circresaha.116.304794 · Cited by 90 · see citing works
Activin and NADPH-oxidase in preeclampsia: insights from in vitro and murine studies
Lim, R., Acharya, R. Y., Delpachitra, P., Hobson, S. R., Sobey, C. G., Drummond, G. R., & Wallace, E. M. (2014) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2014.07.021 · Cited by 87 · see citing works
Self-citationCannabidiol modulation of oxidative stress and signalling
Pereira, S. R., Hackett, B., O’Driscoll, D. N., Sun, M. C., & Downer, E. J. (2021) · Neuronal Signaling · doi:10.1042/ns20200080 · Cited by 90 · see citing works
The pathobiology of diabetic vascular complications—cardiovascular and kidney disease
Gray, S. P., & Jandeleit-Dahm, K. A. M. (2014) · Journal of Molecular Medicine · doi:10.1007/s00109-014-1146-1 · Cited by 83 · see citing works
Silva, T. M. D., Brait, V. H., Drummond, G. R., Sobey, C. G., & Miller, A. A. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028393 · Cited by 78 · see citing works
Self-citationMaiocchi, S. L., Ku, J., Thai, T., Chan, E., Rees, M. D., & Thomas, S. R. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107711 · Cited by 75 · see citing works
Nox1 in cardiovascular diseases: regulation and pathophysiology
Gimenez, M., Schickling, B., Lopes, L. R., & Miller, F. J. (2015) · Clinical Science · doi:10.1042/cs20150404 · Cited by 75 · see citing works
Nitroxyl (HNO) as a Vasoprotective Signaling Molecule
Bullen, M. L., Miller, A. A., Andrews, K. L., Irvine, J. C., Ritchie, R. H., Sobey, C. G., & Kemp‐Harper, B. K. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3327 · Cited by 74 · see citing works
Self-citationMiller, A. A., Silva, T. M. D., Judkins, C. P., Diep, H., Drummond, G. R., & Sobey, C. G. (2010) · Stroke · doi:10.1161/strokeaha.109.575365 · Cited by 74 · see citing works
Self-citationHughes, M., McGettrick, H. M., & Sapey, E. (2020) · European Respiratory Review · doi:10.1183/16000617.0102-2019 · Cited by 73 · see citing works
Opportunity Nox: The Future of NADPH Oxidases as Therapeutic Targets in Cardiovascular Disease
Streeter, J., Thiel, W. H., Brieger, K., & Miller, F. J. (2012) · Cardiovascular Therapeutics · doi:10.1111/j.1755-5922.2011.00310.x · Cited by 73 · see citing works
Hemodynamic Regulation of Reactive Oxygen Species: Implications for Vascular Diseases
Raaz, U., Toh, R., Mäegdefessel, L., Adam, M., Nakagami, F., Emrich, F. C., Spin, J. M., & Tsao, P. S. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2013.5507 · Cited by 73 · see citing works
- Authors
- Judkins, C. P., Diep, H., Broughton, B. R. S., Mast, A. E., Hooker, E. U., Miller, A. A., Selemidis, S., Dusting, G. J., Sobey, C. G., & Drummond, G. R.
- Affiliations
- Monash University (AU)
- The University of Melbourne (AU)
- ORCID
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2010-01
- Volume
- 298
- Issue
- 1
- Pages
- H24-H32
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- OpenAlex
- W2157615046
- Cited by
- 299
- References
- 30
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 12 · 2023: 15 · 2022: 10 · 2021: 16 · 2020: 12 · 2019: 11 · 2018: 15 · 2017: 20 · 2016: 23 · 2015: 30 · 2014: 34 · 2013: 23 · 2012: 25
- FWCI
- 12.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
- PubMed (publishedVersion)
- Research Bank (Australian Catholic University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Keywords
- NOX2, NADPH oxidase, superoxide production, reactive oxygen species, nitric oxide bioavailability, atherosclerosis, atherosclerotic plaque formation, apolipoprotein E deficiency, macrophages, aortic endothelium, high-fat diet
- MeSH terms
- NADPH Oxidase 2, Animals, Aorta, Thoracic, Apolipoproteins E, Biological Availability, Enzyme Inhibitors, Hypercholesterolemia, Immunohistochemistry, Isoenzymes, Lipids, Male, Membrane Glycoproteins, Muscle Contraction, Muscle, Smooth, Vascular, Nitric Oxide, Superoxides, Blotting, Western, Reactive Oxygen Species, Mice, Knockout, NADPH Oxidases, NG-Nitroarginine Methyl Ester, Atherosclerosis, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review