Cited by 291Immune cells in cancerNitric Oxide and Endothelin EffectsRenin-Angiotensin System Studies

The DOI matches its Crossref record; 104 of the 107 references it cites were found in a registry or an index.

Functions of Arginase Isoforms in Macrophage Inflammatory Responses: Impact on Cardiovascular Diseases and Metabolic Disorders

Open access

Yang, Zhihong, Ming, Xiu-Fen·2014·Frontiers in Immunology

DOI 10.3389/fimmu.2014.00533PMC PMC4209887

Open this paper in CoChat — free account Open PDF

Abstract

Macrophages play a paramount role in immunity and inflammation-associated diseases, including infections, cardiovascular diseases, obesity-associated metabolic imbalances, and cancer. Compelling evidence from studies of recent years demonstrates that macrophages are heterogeneous and undergo heterogeneous phenotypic changes in response to microenvironmental stimuli. The M1 killer type response and the M2 repair type response are best known, and are two extreme examples. Among other markers, inducible nitric oxide synthase and type-I arginase (Arg-I), the enzymes that are involved in l-arginine/nitric oxide (NO) metabolism, are associated with the M1 and M2 phenotype, respectively, and therefore widely used as the markers for characterization of the two macrophage phenotypes. There is also a type-II arginase (Arg-II), which is expressed in macrophages and prevalently viewed as having the same function as Arg-I in the cells. In contrast to Arg-I, little information on the role of Arg-II in macrophage inflammatory responses is available. Emerging evidence, however, suggests that differential roles of Arg-I and Arg-II in regulating macrophage functions. In this article, we will review recent developments on the functional roles of the two arginase isoforms in regulation of macrophage inflammatory responses by focusing on their impact on the pathogenesis of cardiovascular diseases and metabolic disorders.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.3389/fimmu.2014.00533

Cites

104 of 104 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

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?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Atherosclerosis--an inflammatory disease
Ross, R. (1999) · New England Journal of Medicine · doi:10.1056/nejm199901143400207 · Cited by 21,725
Exploring the full spectrum of macrophage activation
Mosser, D. M., & Edwards, J. P. (2008) · Nature Reviews Immunology · doi:10.1038/nri2448 · Cited by 9,144 · cited 1×
“, macrophage plasticity, in response to specific signals as a consequence of adaptation to local tissue environmental cues (6, 7).”
Background
Macrophage plasticity and polarization: in vivo veritas
Sica, A., & Mantovani, A. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59643 · Cited by 6,335
Inflammation and insulin resistance
Shoelson, S. E. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29069 · Cited by 4,769
The M1 and M2 paradigm of macrophage activation: Time for reassessment
Martinez, F. O., & Gordon, S. (2014) · F1000Prime Reports · doi:10.12703/p6-13 · Cited by 4,689
Macrophage biology in development, homeostasis and disease
Wynn, T. A., Chawla, A., & Pollard, J. W. (2013) · Nature · doi:10.1038/nature12034 · Cited by 4,684 · cited 3×
“, macrophage plasticity, in response to specific signals as a consequence of adaptation to local tissue environmental cues (6, 7).”
Background
Tumor-Associated Macrophages: From Mechanisms to Therapy
Noy, R., & Pollard, J. W. (2014) · Immunity · doi:10.1016/j.immuni.2014.06.010 · Cited by 4,089
M-1/M-2 Macrophages and the Th1/Th2 Paradigm
Mills, C. D., Kincaid, K., Alt, J. M., Heilman, M. J., & Hill, A. M. (2000) · The Journal of Immunology · doi:10.4049/jimmunol.164.12.6166 · Cited by 3,287 · cited 1×
“Later on, it was characterized that M1 macrophages are more easily activated by LPS to produce cytotoxic NO via iNOS, whereas M2 macrophages generate little NO but more ornithine from the same substrate l-arginine via arginase (15).”
Background
Alternative Activation of Macrophages: An Immunologic Functional Perspective
Martinez, F. O., Helming, L., & Gordon, S. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132532 · Cited by 2,745
Macrophages, inflammation, and insulin resistance
Olefsky, J. M., & Glass, C. K. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135846 · Cited by 2,733
A Lineage of Myeloid Cells Independent of Myb and Hematopoietic Stem Cells
Schulz, C., Perdiguero, E. G., Chorro, L., Szabo-Rogers, H., Cagnard, N., Kierdorf, K., Prinz, M., Wu, B., Jacobsen, S. E. W., Pollard, J. W., et al. (2012) · Science · doi:10.1126/science.1219179 · Cited by 2,578
Nonresolving Inflammation
Nathan, C., & Ding, A. (2010) · Cell · doi:10.1016/j.cell.2010.02.029 · Cited by 2,183 · cited 1×
“NO production from iNOS in M1 macrophages inhibits cell proliferation and kills pathogens, a M1 killing type response (16, 17), while ornithine production promotes cell proliferation and repairs tissue damage through generation of polyamines and collagen in M2 macrophages, a M2 repairing type response (11, 18).”
Background
Monocytes and macrophages: developmental pathways and tissue homeostasis
Ginhoux, F., & Jung, S. (2014) · Nature Reviews Immunology · doi:10.1038/nri3671 · Cited by 1,840
Immune and Inflammatory Mechanisms of Atherosclerosis
Galkina, E., & Ley, K. F. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132620 · Cited by 1,480
Local Macrophage Proliferation, Rather than Recruitment from the Blood, Is a Signature of T H 2 Inflammation
Jenkins, S. J., Rückerl, D., Cook, P. C., Jackson-Jones, L. H., Finkelman, F. D., van Rooijen, N., MacDonald, A. S., & Allen, J. E. (2011) · Science · doi:10.1126/science.1204351 · Cited by 1,404 · cited 1×
“Moreover, tissue macrophages are not terminally differentiated and are maintained throughout life by local proliferative selfrenewal (4,5).”
Background
Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata
Świrski, F. K., Libby, P., Aïkawa, E., Alcaide, P., Luscinskas, F. W., Weissleder, R., & Pittet, M. J. (2007) · Journal of Clinical Investigation · doi:10.1172/jci29950 · Cited by 1,308
Emerging regulation and functions of autophagy
Boya, P., Reggiori, F., & Codogno, P. (2013) · Nature Cell Biology · doi:10.1038/ncb2788 · Cited by 1,216 · cited 1×
“Moreover, we also show that Arg-II negatively regulates autophagy function – a cell protective mechanism of lysosomal proteolysis aiming to remove harmful proteins (79) – in endothelial cells, which is also independent on its l-arginine–urea hydrolase activity [Ref.”
Background
M1 and M2 Macrophages: Oracles of Health and Disease
Mills, C. D. (2012) · Critical Reviews in Immunology · doi:10.1615/critrevimmunol.v32.i6.10 · Cited by 1,169
Local proliferation dominates lesional macrophage accumulation in atherosclerosis
Robbins, C. S., Hilgendorf, I., Weber, G. F., Theurl, I., Iwamoto, Y., Figueiredo, J.-L., Gorbatov, R., Sukhova, G. K., Gerhardt, L. M. S., Smyth, D., et al. (2013) · Nature Medicine · doi:10.1038/nm.3258 · Cited by 1,041 · cited 1×
“Moreover, tissue macrophages are not terminally differentiated and are maintained throughout life by local proliferative selfrenewal (4,5).”
Background
L-arginine is required for expression of the activated macrophage effector mechanism causing selective metabolic inhibition in target cells.
Hibbs, J. B., Vavrin, Z., & Taintor, R. R. (1987) · The Journal of Immunology · doi:10.4049/jimmunol.138.2.550 · Cited by 938 · cited 1×
“NO production from iNOS in M1 macrophages inhibits cell proliferation and kills pathogens, a M1 killing type response (16, 17), while ornithine production promotes cell proliferation and repairs tissue damage through generation of polyamines and collagen in M2 macrophages, a M2 repairing type response (11, 18).”
Background
Arginase-1–Expressing Macrophages Suppress Th2 Cytokine–Driven Inflammation and Fibrosis
Pesce, J. T., Ramalingam, T. R., Mentink-Kane, M. M., Wilson, M. S., El Kasmi, K. C., Smith, A. M., Thompson, R. W., Cheever, A. W., Murray, P. J., & Wynn, T. A. (2009) · PLoS Pathogens · doi:10.1371/journal.ppat.1000371 · Cited by 816 · cited 1×
“However, mice with specific Arg-I gene deficiency in macrophages show exacerbated Th2 response and fibrosis in the liver of Schistosoma mansoni infected mice (65), which does not seem to support previous suggestions in promotion of Th2 responses (63).”
Background
Ablation of CD11c-Positive Cells Normalizes Insulin Sensitivity in Obese Insulin Resistant Animals
Patsouris, D., Li, P.-P., Thapar, D., Chapman, J., Olefsky, J. M., & Neels, J. G. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.08.015 · Cited by 804
Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac–derived macrophages
Hoeffel, G., Wang, Y., Greter, M., See, P., Teo, P., Malleret, B., Leboeuf, M., Low, D., Oller, G., Almeida, F., et al. (2012) · Journal of Experimental Medicine · doi:10.1084/jem.20120340 · Cited by 786
R EGULATION OF E NZYMES OF THE U REA C YCLE AND A RGININE M ETABOLISM
Morris, S. M. (2002) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.22.110801.140547 · Cited by 736 · cited 1×
“2 mmol/L) far exceed the Km of eNOS (2– 20 μmol/L) (67).”
Background
Differential Regulation of Nitric Oxide Synthase-2 and Arginase-1 by Type 1/Type 2 Cytokines In Vivo: Granulomatous Pathology Is Shaped by the Pattern of l -Arginine Metabolism
Hesse, M., Modolell, M., Flamme, A. C. L., Schito, M. L., Fuentes, J. M., Cheever, A. W., Pearce, E. J., & Wynn, T. A. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.11.6533 · Cited by 723
Nitric oxide synthase generates superoxide and nitric oxide in arginine-depleted cells leading to peroxynitrite-mediated cellular injury.
Xia, Y., Dawson, V. L., Dawson, T. M., Snyder, S. H., & Zweier, J. L. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.13.6770 · Cited by 717 · cited 1×
“The best characterization of Arg-II function is done in vascular endothelial cells in which the isoenzyme, similar to Arg-I, metabolizes l-arginine to urea and lornithine, which limits l-arginine bioavailability for generation of the vasoprotective NO via eNOS, resulting in vascular endothelial dysfunction (33, 34).”
Background
Arginine Metabolism: Boundaries of Our Knowledge
Morris, S. M. (2007) · Journal of Nutrition · doi:10.1093/jn/137.6.1602s · Cited by 649
Alternative Metabolic States in Murine Macrophages Reflected by the Nitric Oxide Synthase/Arginase Balance: Competitive Regulation by CD4+ T Cells Correlates with Th1/Th2 Phenotype
Munder, M., Eichmann, K., & Modolell, M. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.160.11.5347 · Cited by 647
Toll-like receptor–induced arginase 1 in macrophages thwarts effective immunity against intracellular pathogens
El Kasmi, K. C., Qualls, J. E., Pesce, J. T., Smith, A. M., Thompson, R. W., Henao-Tamayo, M., Basaraba, R. J., König, T., Schleicher, U., Koo, M.-S., et al. (2008) · Nature Immunology · doi:10.1038/ni.1671 · Cited by 646
Pro-Inflammatory CD11c+CD206+ Adipose Tissue Macrophages Are Associated With Insulin Resistance in Human Obesity
Wentworth, J. M., Naselli, G., Brown, W. A., Doyle, L., Phipson, B., Smyth, G. K., Wabitsch, M., O’Brien, P. E., & Harrison, L. C. (2010) · Diabetes · doi:10.2337/db09-0287 · Cited by 636
Th1/Th2-regulated expression of arginase isoforms in murine macrophages and dendritic cells.
Munder, M., Eichmann, K., Morán, J., Centeno, F., Soler, G., & Modolell, M. (1999) · Journal of Immunology · doi:10.4049/jimmunol.163.7.3771 · Cited by 619
Comparative properties of arginases
Jenkinson, C. P., Grody, W. W., & Cederbaum, S. D. (1996) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/0305-0491(95)02138-8 · Cited by 610 · cited 2×
“Although both Arg-I and ArgII are to hydrolyze l-arginine to produce urea and l-ornithine (25), the functional impact of the two isoenzymes is either similar or different depending on specific organs/cells.”
Background
Macrophage plasticity in experimental atherosclerosis
Khallou-Laschet, J., Varthaman, A., Fornasa, G., Compain, C., Gaston, A.-T., Clement, M., Dussiot, M., Levillain, O., Graff-Dubois, S., Nicoletti, A., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008852 · Cited by 517 · cited 2×
“The expression of Arg-I and Arg-II is inducible in macrophages depending on external stimuli (42, 43).”
BackgroundResult
M1 and M2 Macrophages: The Chicken and the Egg of Immunity
Mills, C. D., & Ley, K. F. (2014) · Journal of Innate Immunity · doi:10.1159/000364945 · Cited by 422 · cited 1×
“In contrast, M2 macrophages produce more anti-inflammatory cytokines and substances involved in repairing function, typically, arginase/ornithine, EGF, VEGF, and TGF-β, and mannose receptor (9).”
Background
Regulatory role of arginase I and II in nitric oxide, polyamine, and proline syntheses in endothelial cells
Li, H. Z., Meininger, C. J., Hawker, J. R., Haynes, T. E., Kepka‐Lenhart, D., Mistry, S. K., Morris, S. M., & Wu, G. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.280.1.e75 · Cited by 395 · cited 1×
“While the cell proliferation– stimulating effect of Arg-II is dependent on its l-arginine–urea hydrolase activity via synthesis of ornithine and polyamines (71, 78), the cell apoptosis/senescence-promoting effect is independent of its enzymatic activity (Figure 3).”
Background
Diabetes-induced Coronary Vascular Dysfunction Involves Increased Arginase Activity
Romero, M. J., Platt, D. H., Tawfik, H. E., Labazi, M., El‐Remessy, A. B., Bartoli, M., Caldwell, R. B., & Caldwell, R. W. (2007) · Circulation Research · doi:10.1161/circresaha.107.155028 · Cited by 386 · cited 1×
“expression in porcine coronary arterioles in response to hydrogen peroxide (H2O2) and peroxynitrite (92) and Arg-II (but not Arg-I) expression and/or activity in women with preeclampsia (93) and in human endothelial cells in response to thrombin (35), oxidized LDL (94), and hyperglycemia (36).”
Background
Cutting Edge: Stat6-Dependent Substrate Depletion Regulates Nitric Oxide Production
Rutschman, R., Lang, R., Hesse, M., Ihle, J. N., Wynn, T. A., & Murray, P. J. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.4.2173 · Cited by 331
Arginase and polyamine synthesis are key factors in the regulation of experimental leishmaniasis in vivo
Kropf, P., Fuentes, J. M., Fähnrich, E., Arpa, L., Herath, S., Weber, V., Soler, G., Celada, A., Modolell, M., & Müller, I. (2005) · The FASEB Journal · doi:10.1096/fj.04-3416fje · Cited by 295
Translational evidence that impaired autophagy contributes to arterial ageing
LaRocca, T. J., Henson, G. D., Thorburn, A. M., Sindler, A. L., Pierce, G. L., & Seals, D. R. (2012) · The Journal of Physiology · doi:10.1113/jphysiol.2012.229690 · Cited by 258
Association of plasma asymmetrical dimethylarginine (ADMA) with elevated vascular superoxide production and endothelial nitric oxide synthase uncoupling: implications for endothelial function in human atherosclerosis
Antoniades, C. A., Shirodaria, C. C., Leeson, P., Antonopoulos, A. S., Warrick, N., Van-Assche, T., Cunnington, C., Tousoulis, D., Pillai, R. G., Ratnatunga, C., et al. (2009) · European Heart Journal · doi:10.1093/eurheartj/ehp061 · Cited by 258
Enhancer-Mediated Control of Macrophage-Specific Arginase I Expression
Pauleau, A., Rutschman, R., Lang, R., Pernis, A. B., Watowich, S. S., & Murray, P. J. (2004) · The Journal of Immunology · doi:10.4049/jimmunol.172.12.7565 · Cited by 247 · cited 2×
“, by Th2 cytokines IL-4 and IL-13 (44, 61, 62).”
Arginase inhibition restores NOS coupling and reverses endothelial dysfunction and vascular stiffness in old rats
Kim, J. H., Bugaj, L. J., Oh, Y. J., Bivalacqua, T. J., Ryoo, S., Soucy, K. G., Santhanam, L., Webb, A. K., Camara, A., Sikka, G., et al. (2009) · Journal of Applied Physiology · doi:10.1152/japplphysiol.91393.2008 · Cited by 244 · cited 1×
“The best characterization of Arg-II function is done in vascular endothelial cells in which the isoenzyme, similar to Arg-I, metabolizes l-arginine to urea and lornithine, which limits l-arginine bioavailability for generation of the vasoprotective NO via eNOS, resulting in vascular endothelial dysfunction (33, 34).”
Background
l -Arginine Supplementation in Peripheral Arterial Disease: No Benefit and Possible Harm
Wilson, A. M., Harada, R., Nair, N., Balasubramanian, N., & Cooke, J. P. (2007) · Circulation · doi:10.1161/circulationaha.106.683656 · Cited by 241
Thrombin Stimulates Human Endothelial Arginase Enzymatic Activity via RhoA/ROCK Pathway
Ming, X., Barandiér, C., Viswambharan, H., Kwak, B. R., Mach, F., Mazzolai, L., Hayoz, D., Ruffieux, J., Rusconi, S., Montani, J., et al. (2004) · Circulation · doi:10.1161/01.cir.0000142867.26182.32 · Cited by 240
Molecular cloning of cDNA for nonhepatic mitochondrial arginase (arginase II) and comparison of its induction with nitric oxide synthase in a murine macrophage‐like cell line
Gotoh, T., Sonoki, T., Nagasaki, A., Terada, K., Takiguchi, M., & Mori, M. (1996) · FEBS Letters · doi:10.1016/0014-5793(96)01015-0 · Cited by 236 · cited 2×
“Unlike Arg-I, Arg-II is confined mainly to kidney, brain, prostate, intestine, and also pancreas (22, 23, 32).”
Background
Targeting the Shift from M1 to M2 Macrophages in Experimental Autoimmune Encephalomyelitis Mice Treated with Fasudil
Liu, C., Lǐ, Y., Yu, J., Ling, F., Hou, S., Liu, Y., Guo, M., Xie, Y., Meng, J., Zhang, H., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054841 · Cited by 233 · cited 1×
“In macrophages, however, ROCK kinase inhibitor enhances Arg-I expression and shift M1 to M2 phenotype (95), suggesting that ROCK pathway may inhibit Arg-I expression.”
Background
Human type II arginase: sequence analysis and tissue-specific expression
Morris, S. M., Bhamidipati, D., & Kepka‐Lenhart, D. (1997) · Gene · doi:10.1016/s0378-1119(97)00099-1 · Cited by 216
Macrophage arginine metabolism and the inhibition or stimulation of cancer
Mills, C. D., Shearer, J. D., Evans, R. L., & Caldwell, M. D. (1992) · The Journal of Immunology · doi:10.4049/jimmunol.149.8.2709 · Cited by 191 · cited 1×
“In particular, monocytes and macrophages are recruited into tumors and regulate tumor growth by changing their functional phenotypes, which is originally demonstrated by Mills and colleagues (100).”
Background
Induction of arginase I transcription by IL-4 requires a composite DNA response element for STAT6 and C/EBPβ
Gray, M. J., Poljakovic, M., Kepka-Lenhart, D., & Morris, S. M. (2005) · Gene · doi:10.1016/j.gene.2005.04.004 · Cited by 191 · cited 2×
“, by Th2 cytokines IL-4 and IL-13 (44, 61, 62).”
Cloning and Characterization of the Human Type II Arginase Gene
Vockley, J. G., Jenkinson, C. P., Shukla, H., Kern, R. M., Grody, W. W., & Cederbaum, S. D. (1996) · Genomics · doi:10.1006/geno.1996.0606 · Cited by 191 · cited 2×
“Unlike Arg-I, Arg-II is confined mainly to kidney, brain, prostate, intestine, and also pancreas (22, 23, 32).”
Background
Autophagy in Atherosclerosis
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
Inducible NO Synthase–DependentS-Nitrosylation and Activation of Arginase1 Contribute to Age-Related Endothelial Dysfunction
Santhanam, L., Lim, H. K., Lim, H. K., Miriel, V. A., Brown, T. R., Patel, M. D., Balanson, S., Ryoo, S., Anderson, M., Irani, K., et al. (2007) · Circulation Research · doi:10.1161/circresaha.107.157727 · Cited by 188 · cited 1×
“For example, increased activity and/or expression of either Arg-I or Arg-II in endothelial cells impair the vasoprotective endothelial NO production via eNOS (27).”
Background
Arginase Inhibition Improves Endothelial Function in Patients With Coronary Artery Disease and Type 2 Diabetes Mellitus
Shemyakin, A. S., Kövamees, O., Rafnsson, A. T., Böhm, F., Svenarud, P. K., Settergren, M., Jung, C., & Pernow, J. (2012) · Circulation · doi:10.1161/circulationaha.112.140335 · Cited by 185
Mouse Model for Human Arginase Deficiency
Iyer, R. K., Yoo, P. K., Kern, R. M., Rozengurt, N., Tsoa, R. W., O’Brien, W. E., Yu, H., Grody, W. W., & Cederbaum, S. D. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.13.4491-4498.2002 · Cited by 171 · cited 2×
“The vital effect of hepatic Arg-I is evidenced by the studies showing that Arg-I knockout mice reveal severe symptoms of hyperammonemia and die between postnatal days 10 and 14 (31).”
Background
Arginase and vascular aging
Santhanam, L., Christianson, D. W., Nyhan, D. P., & Berkowitz, D. E. (2008) · Journal of Applied Physiology · doi:10.1152/japplphysiol.90627.2008 · Cited by 166 · cited 1×
“Another alternative hypothesis is that a specific intracellular pool of l-arginine for NO production may exist in endothelial cells and could be depleted by enhanced arginase (73), yet, it is highly speculative.”
Background
Hyperactive S6K1 Mediates Oxidative Stress and Endothelial Dysfunction in Aging: Inhibition by Resveratrol
Rajapakse, A. G., Yepuri, G., Carvas, J. M., Stein, S., Matter, C. M., Scerri, I., Ruffieux, J., Montani, J., Ming, X., & Yang, Z. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019237 · Cited by 164
Arginase II Promotes Macrophage Inflammatory Responses Through Mitochondrial Reactive Oxygen Species, Contributing to Insulin Resistance and Atherogenesis
Ming, X., Rajapakse, A. G., Yepuri, G., Xiong, Y., Carvas, J. M., Ruffieux, J., Scerri, I., Wu, Z., Popp, K., Li, J., et al. (2012) · Journal of the American Heart Association · doi:10.1161/jaha.112.000992 · Cited by 155 · cited 9×
“Arg-II−/−mice, when fed a HFD, although have similar body weight as WT controls, reveal lower fasting plasma glucose concentration, are more glucose tolerant and insulin sensitive (43) as compared to WT mice on HFD.”
BackgroundMethodInfluential
Pivotal Advance: Arginase-1-independent polyamine production stimulates the expression of IL-4-induced alternatively activated macrophage markers while inhibiting LPS-induced expression of inflammatory genes
den Bossche, J. V., Lamers, W. H., Köhler, E. S., Geuns, J. M. C., Alhonen, L. I., Uimari, A., Pirnes-Karhu, S., Overmeire, E. V., Morias, Y., Brys, L., et al. (2012) · Journal of Leukocyte Biology · doi:10.1189/jlb.0911453 · Cited by 145
Molecular cloning and nucleotide sequence of cDNA for human liver arginase.
Haraguchi, Y., Takiguchi, M., Amaya, Y., Kawamoto, S., Matsuda, I., & Mori, M. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.2.412 · Cited by 143 · cited 1×
“The primary function of Arg-I is to remove excessive nitrogen produced from amino acid metabolism through hepatic urea cycle, which is otherwise toxic for our body (28, 29), because Arg-I is constitutively and abundantly expressed as a cytosolic enzyme in the liver (30).”
Background
Hyperargininemia due to liver arginase deficiency
Crombez, E. A., & Cederbaum, S. D. (2004) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2004.11.004 · Cited by 135 · cited 2×
“Patients with Arg-I deficiency due to gene mutation reveal urea cycle disorder, hyperargininemia, and exhibit progressive neurologic impairment, development retardation, and hepatic dysfunction associated with cirrhosis and carcinoma in early childhood (28, 29).”
Background
Arginase: The Emerging Therapeutic Target for Vascular Oxidative Stress and Inflammation
Yang, Z., & Ming, X. (2013) · Frontiers in Immunology · doi:10.3389/fimmu.2013.00149 · Cited by 133
Positive crosstalk between arginase‐II and S6K1 in vascular endothelial inflammation and aging
Yepuri, G., Velagapudi, S., Xiong, Y., Rajapakse, A. G., Montani, J., Ming, X., & Yang, Z. (2012) · Aging Cell · doi:10.1111/acel.12001 · Cited by 129 · cited 8×
“Interestingly, silencing Arg-II gene in senescent endothelial cells or deficiency in Arg-II gene in mice reduces S6K1 activity, recouples eNOS function in aging, and inhibits endothelial expression of adhesion molecules such as ICAM-1 and VCAM-1, resulting in inhibition of monocyte-endothelial cell interaction, demons…”
BackgroundInfluential
OxLDL-dependent activation of arginase II is dependent on the LOX-1 receptor and downstream RhoA signaling
Ryoo, S., Bhunia, A. K., Chang, F., Shoukas, A. A., Berkowitz, D. E., & Romer, L. H. (2010) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2010.10.044 · Cited by 127 · cited 3×
“Silencing Arg-II gene in human monocyte/macrophage cell lines decreases the cell adhesion to endothelial cells with reduced production of pro-inflammatory cytokines in response to LPS or ox-LDL at both the mRNA and protein levels.”
Background
Up‐regulation of arginase activity contributes to attenuated reflex cutaneous vasodilatation in hypertensive humans
Holowatz, L. A., & Kenney, W. L. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.128959 · Cited by 117
Insulin and the arginine paradox.
Kurz, S. D., & Harrison, D. G. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119166 · Cited by 112 · cited 1×
“Even though, acute l-arginine supplementation in cells, isolated blood vessels, or in animals or in patients is able to enhance NO production and improve endothelium-dependent relaxations, a situation called “arginine paradox” (68, 69).”
Background
Arginase contributes to endothelial cell oxidative stress in response to plasma from women with preeclampsia
Sankaralingam, S., Xu, H., & Davidge, S. T. (2009) · Cardiovascular Research · doi:10.1093/cvr/cvp277 · Cited by 105 · cited 1×
“expression in porcine coronary arterioles in response to hydrogen peroxide (H2O2) and peroxynitrite (92) and Arg-II (but not Arg-I) expression and/or activity in women with preeclampsia (93) and in human endothelial cells in response to thrombin (35), oxidized LDL (94), and hyperglycemia (36).”
Background
Control of Nitric Oxide Production by Transforming Growth Factor-β1: Mechanistic Insights and Potential Relevance to Human Disease
Yoram Vodovotz, B. (1997) · Nitric Oxide · doi:10.1006/niox.1996.0105 · Cited by 104
The Arginase II Gene Is an Anti-inflammatory Target of Liver X Receptor in Macrophages
Marathe, C., Bradley, M. N., Hong, C., López, F., de Galarreta, C. M. R., Tontonoz, P., & Castrillo, A. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m605237200 · Cited by 102 · cited 1×
“An early study showed that Arg-II gene is a direct target of liver X receptor that has been shown to exert inhibitory effects on expression of inflammatory genes in macrophages (49).”
Background
Arginase I: a limiting factor for nitric oxide and polyamine synthesis by activated macrophages?
Kepka‐Lenhart, D., Mistry, S. K., Wu, G., & Morris, S. M. (2000) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.2000.279.6.r2237 · Cited by 99
To Give or Not to Give? Lessons from the Arginine Paradox
Dioguardi, F. S. (2011) · Lifestyle Genomics · doi:10.1159/000327777 · Cited by 95 · cited 1×
“These studies do not support a role of absolute l-arginine deficiency caused by arginase, but strongly implicate that too much l-arginine is even harmful, which is probably due to production of other undesired metabolites from l-arginine as speculated (76).”
Background
Upregulation of Arginase by H2O2Impairs Endothelium-Dependent Nitric Oxide-Mediated Dilation of Coronary Arterioles
Thengchaisri, N., Hein, T. W., Wang, W., Xu, X. Y., Li, Z., Fossum, T. W., & Kuo, L. (2006) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000233334.24805.62 · Cited by 94
Arginase‐II Induces Vascular Smooth Muscle Cell Senescence and Apoptosis Through p66Shc and p53 Independently of Its l ‐Arginine Ureahydrolase Activity: Implications for Atherosclerotic Plaque Vulnerability
Xiong, Y., Yu, Y., Montani, J., Yang, Z., & Ming, X. (2013) · Journal of the American Heart Association · doi:10.1161/jaha.113.000096 · Cited by 91
Chromosomal Localization of the Human Arginase II Gene and Tissue Distribution of Its mRNA
Gotoh, T., Araki, M., & Mori, M. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6473 · Cited by 90
Hypoxia promotes human pulmonary artery smooth muscle cell proliferation through induction of arginase
Chen, B., Calvert, A. E., Cui, H., & Nelin, L. D. (2009) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00183.2009 · Cited by 88 · cited 1×
“While the cell proliferation– stimulating effect of Arg-II is dependent on its l-arginine–urea hydrolase activity via synthesis of ornithine and polyamines (71, 78), the cell apoptosis/senescence-promoting effect is independent of its enzymatic activity (Figure 3).”
Background
Autophagy in obesity and atherosclerosis: Interrelationships between cholesterol homeostasis, lipoprotein metabolism and autophagy in macrophages and other systems
Ouimet, M. I. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2013.03.007 · Cited by 86
Isolation of human liver arginase cdna and demonstration of nonhomology between the two human arginase genes
Dizikes, G. J., Grody, W. W., Kern, R. M., & Cederbaum, S. D. (1986) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(86)80333-3 · Cited by 83
Transcriptional regulation of macrophage arginase 1 expression and its role in atherosclerosis
Pourcet, B., & Pineda‐Torra, I. (2013) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2012.10.003 · Cited by 82 · cited 1×
“The complexity of Arg-I gene regulation mechanisms are further complicated by the fact that these transcription factors can be regulated by post-translational modification mechanisms such as SUMOylation and ubiquitination that are participating in the regulation of Arg-1 gene [for detailed description of these mechani…”
Background
Regulation of Arginine Availability and Its Impact on NO Synthesis
Morris, S. M. (2000) · Elsevier eBooks · doi:10.1016/b978-012370420-7/50012-5 · Cited by 75
The gene for human liver arginase (ARG1) is assigned to chromosome band 6q23.
Sparkes, R. S., Dizikes, G. J., Klisak, I. J., Grody, W. W., Mohandas, T. K., Heinzmann, C., Zollman, S., Lusis, A. J., & Cederbaum, S. D. (1986) · PubMed · Cited by 72
Local tetrahydrobiopterin administration augments reflex cutaneous vasodilation through nitric oxide-dependent mechanisms in aged human skin
Stanhewicz, A. E., Bruning, R. S., Smith, C. J. W., Kenney, W. L., & Holowatz, L. A. (2011) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01257.2011 · Cited by 70
Immunohistochemical study of arginase 1 and 2 in various tissues of rats
Choi, S., Park, C., Ahn, M., Lee, J. H., & Shin, T. (2011) · Acta Histochemica · doi:10.1016/j.acthis.2011.09.002 · Cited by 70 · cited 2×
“Arg-I has been reported to be expressed also in many extrahepatic tissues such as stomach, pancreas, and lung (32).”
Background
In vivo veritas
Zitvogel, L., & Tursz, T. (2005) · Nature Biotechnology · doi:10.1038/nbt1105-1372 · Cited by 65 · cited 1×
“This phenotypic cell is mainly participating in resolution of inflammation, tissue repairing, angiogenesis, allergy, and tumor progression (10).”
Background
Age-Related Alteration of Arginase Activity Impacts on Severity of Leishmaniasis
Müller, I., Hailu, A., Choi, B., Abebe, T., Fuentes, J. M., Munder, M., Modolell, M., & Kropf, P. (2008) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0000235 · Cited by 60
Increased arginase II activity contributes to endothelial dysfunction through endothelial nitric oxide synthase uncoupling in aged mice
Shin, W., Berkowitz, D. E., & Ryoo, S.-W. (2012) · Experimental & Molecular Medicine · doi:10.3858/emm.2012.44.10.068 · Cited by 57
Arginase induction promotes Trypanosoma cruzi intracellular replication in Cruzipain‐treated J774 cells through the activation of multiple signaling pathways
Stempin, C. C., Tanos, T., Coso, O. A., & Cerbán, F. M. (2003) · European Journal of Immunology · doi:10.1002/eji.200324313 · Cited by 57 · cited 1×
“The stress sensor p38mapk has been demonstrated to participate in up-regulation of activity and expression of Arg-I and Arg-II in macrophages (85, 86).”
Background
p38 mitogen-activated protein kinase is involved in arginase-II-mediated eNOS-Uncoupling in Obesity
Yu, Y., Rajapakse, A. G., Montani, J., Yang, Z., & Ming, X. (2014) · Cardiovascular Diabetology · doi:10.1186/s12933-014-0113-z · Cited by 56 · cited 2×
“Our most recent study provides evidence showing that p38mapk also functions as downstream effector of Arg-II in endothelial cells, causing oxidative stress through eNOS-uncoupling, since overexpression of Arg-II in human endothelial cells causes eNOS-uncoupling and augments p38mapk activation (90), and inhibition of p…”
Background
p38 Mitogen-Activated Protein Kinase (MAPK) Increases Arginase Activity and Contributes to Endothelial Dysfunction in Corpora Cavernosa from Angiotensin-II-Treated Mice
Toque, H. A., Romero, M. J., Tostes, R. C., Shatanawi, A., Chandra, S., Carneiro, Z. N., Inscho, E. W., Webb, R. C., Caldwell, R. B., & Caldwell, R. W. (2010) · The Journal of Sexual Medicine · doi:10.1111/j.1743-6109.2010.01996.x · Cited by 52
Xanthine Oxidoreductase Promotes the Inflammatory State of Mononuclear Phagocytes through Effects on Chemokine Expression, Peroxisome Proliferator-activated Receptor-γ Sumoylation, and HIF-1α
Gibbings, S. L., Elkins, N. D., Fitzgerald, H., Tiao, J., Weyman, M. E., Shibao, G. N., Fini, M. A., & Wright, R. M. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.150847 · Cited by 52 · cited 1×
“The complexity of Arg-I gene regulation mechanisms are further complicated by the fact that these transcription factors can be regulated by post-translational modification mechanisms such as SUMOylation and ubiquitination that are participating in the regulation of Arg-1 gene [for detailed description of these mechani…”
Background
Arginase I Attenuates Inflammatory Cytokine Secretion Induced by Lipopolysaccharide in Vascular Smooth Muscle Cells
Wang, X., Chen, Y., Qin, W., Zhang, W., Wei, S., Wang, J., Liu, F. Q., Gong, L., An, F. S., Zhang, Y., et al. (2011) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.229302 · Cited by 52 · cited 1×
“A study in human smooth muscle cells showing that overexpression of Arg-I gene is able to decrease LPS-induced pro-inflammatory cytokine production (64), seems to support the”
Background
Cloning of rat liver arginase cDNA and elucidation of regulation of arginase gene expression in H4 rat hepatoma cells
Dizikes, G. J., Spector, E., & Cederbaum, S. D. (1986) · Somatic Cell and Molecular Genetics · doi:10.1007/bf01570732 · Cited by 47
Direct Activation of Murine Peritoneal Macrophages for Nitric Oxide Production and Tumor Cell Killing by Interferon-γ
Dileepan, K. N., PAGE, J. C., Li, Y., & Stechschulte, D. J. (1995) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.1995.15.387 · Cited by 46 · cited 1×
“L-ARGININE METABOLISM, iNOS, AND ARGINASE IN MACROPHAGE FUNCTIONAL POLARIZATION The suggestion that l-arginine metabolism could be involved in regulation of macrophage phenotypes was from early studies with macrophages isolated from the Th1 strain mouse C57B1/6 and Th2 strain BALB/c mouse (13, 14).”
Background
Paradoxical effect of l-arginine: Acceleration of endothelial cell senescence
Scalera, F., Closs, E. I., Flick, E., Martens‐Lobenhoffer, J., Boissel, J., Lendeckel, U., Heimburg, A., & Bode‐Böger, S. M. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.06.091 · Cited by 45
Long term exposure to L-arginine accelerates endothelial cell senescence through arginase-II and S6K1 signaling
Xiong, Y., Forbiteh, M., Yu, Y., Montani, J., Ming, X., & Yang, Z. (2014) · Aging · doi:10.18632/aging.100663 · Cited by 45 · cited 4×
“Even though, acute l-arginine supplementation in cells, isolated blood vessels, or in animals or in patients is able to enhance NO production and improve endothelium-dependent relaxations, a situation called “arginine paradox” (68, 69).”
BackgroundInfluential
Purification of rat kidney arginases A1 and A4 and their subcellular distribution.
Skrzypek-Osiecka, I., Robin, Y., & Porembska, Z. (1983) · PubMed · Cited by 44
Low response of BALB/c macrophages to priming and activating signals
Oswald, I. P., Afroun, S., Bray, D. H., Petit, J. F., & Lemaire, G. (1992) · Journal of Leukocyte Biology · doi:10.1002/jlb.52.3.315 · Cited by 44 · cited 1×
“L-ARGININE METABOLISM, iNOS, AND ARGINASE IN MACROPHAGE FUNCTIONAL POLARIZATION The suggestion that l-arginine metabolism could be involved in regulation of macrophage phenotypes was from early studies with macrophages isolated from the Th1 strain mouse C57B1/6 and Th2 strain BALB/c mouse (13, 14).”
Background
Thrombin induces endothelial arginase through AP-1 activation
Zhu, W., Chandrasekharan, U. M., Bandyopadhyay, S., Morris, S. M., DiCorleto, P. E., & Kashyap, V. S. (2009) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00466.2009 · Cited by 37 · cited 1×
“This seems to be also the case in bovine and rat aortic endothelial cells for Arg-I expression (87) and in human endothelial cells and mouse penile tissues for Arg-II (88, 89).”
Background
Protein Tyrosine Phosphatase SHP2 Mediates Chronic Insulin-Induced Endothelial Inflammation
Giri, H., Muthuramu, I., Dhar, M., Rathnakumar, K., Ram, U., & Dixit, M. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.111.239251 · Cited by 37 · cited 1×
“This seems to be also the case in bovine and rat aortic endothelial cells for Arg-I expression (87) and in human endothelial cells and mouse penile tissues for Arg-II (88, 89).”
Background
Selective Endothelial Overexpression of Arginase II Induces Endothelial Dysfunction and Hypertension and Enhances Atherosclerosis in Mice
Vaisman, B. L., Andrews, K. L., Khong, S. M. L., Wood, K. C., Moore, X. L., Fu, Y., Kepka‐Lenhart, D., Morris, S. M., Remaley, A. T., & Chin-Dusting, J. P. F. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039487 · Cited by 35 · cited 1×
“Arg-II as therapeutic target in chronic inflammatory disorders such as age-associated vascular dysfunctions, atherosclerosis, and type-II diabetes and complications has shown promising beneficial effects in genetic modified mouse models (39, 43, 96).”
Background
Arginase Deficiency With New Phenotype and a Novel Mutation: Contemporary Summary
Tsang, J. P. K., Poon, W. L., Luk, H., Fung, C. W., Ching, C. K., Mak, C. M., Lam, C. W., Siu, T. S., Tam, S., & Wong, V. C. N. (2012) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2012.06.012 · Cited by 35
Exogenous Nitric Oxide Inhibits VCAM-1 Expression in Human Peritoneal Mesothelial Cells
Lee, S. K., Kim, J. H., Yang, W. S., Kim, S. B., Park, S.-K., & Park, J. S. (2002) · The Nephron journals/Nephron journals · doi:10.1159/000054733 · Cited by 33
Interferon‐γ priming is involved in the activation of arginase by oligodeoxinucleotides containing CpG motifs in murine macrophages
Liscovsky, M. V., Ranocchia, R. P., Gorlino, C. V., Alignani, D., Morón, G., Maletto, B. A., & Pistoresi-Palencia, M. C. (2008) · Immunology · doi:10.1111/j.1365-2567.2008.02938.x · Cited by 29 · cited 1×
“The stress sensor p38mapk has been demonstrated to participate in up-regulation of activity and expression of Arg-I and Arg-II in macrophages (85, 86).”
Background
New Role for L-Arginine in Regulation of Inducible Nitric-Oxide-Synthase-Derived Superoxide Anion Production in Raw 264.7 Macrophages
Pekarová, M., Lojek, A., Martiskova, H., Vašíček, O., Binó, L., Klinke, A., Lau, D., Kuchta, R., Kadlec, J., Vrba, R., et al. (2011) · The Scientific World JOURNAL · doi:10.1100/2011/321979 · Cited by 28
Induction of Intracellular Arginase Activity Does not Diminish the Capacity of Macrophages to Produce Nitric Oxide in vitro
Fliggeri, J., Jungi, T. W., & Blum, J. W. (1999) · Immunobiology · doi:10.1016/s0171-2985(99)80068-0 · Cited by 23
Time for Reassessment
Starey, C. J. H. (1966) · BMJ · doi:10.1136/bmj.2.5514.646-f · Cited by 14

Flagged first, then by citations

3 of the 107 references couldn’t be matched to a known paper.

Sorted by citations

Arginase: A Multifaceted Enzyme Important in Health and Disease
Caldwell, R. W., Rodriguez, P. C., Toque, H. A., Narayanan, S. P., & Caldwell, R. B. (2018) · Physiological Reviews · doi:10.1152/physrev.00037.2016 · Cited by 495
“For instance, arginase-induced increases in polyamines and proline production can lead to thickening, fibrosis, and stiffening of blood vessels and airways, hypertrophy and fibrosis of the heart and kidneys, neurodegeneration, and growth of tumors (51, 127, 164, 238).”
Background
Arginase: an old enzyme with new tricks
Caldwell, R. B., Toque, H. A., Narayanan, S. P., & Caldwell, R. W. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.03.006 · Cited by 358
Arginine and Endothelial Function
Gambardella, J., Khondkar, W., Morelli, M. B., Wang, X., Santulli, G., & Trimarco, V. (2020) · Biomedicines · doi:10.3390/biomedicines8080277 · Cited by 266
The PI3K/Akt Pathway in Meta-Inflammation
Acosta‐Martínez, M., & Cabail, M. Z. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232315330 · Cited by 259
“Arginase 1 is one of the hallmarks of alternatively activated macrophages and contributes to the resolution of inflammation and tissue repair by degrading arginine and preventing the generation of cytotoxic nitric oxide [79].”
Background
Deciphering the performance of macrophages in tumour microenvironment: a call for precision immunotherapy
Toledo, B., Chen, L. Z., Paniagua-Sancho, M., Marchal, J. A., Perán, M., & Giovannetti, E. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01559-0 · Cited by 255

See all 291

Authors: Yang, Z., & Ming, X.-F.
Affiliations: University of Fribourg (CH)
Corresponding author: Yang, Zhihong
Ming, Xiu-Fen
ORCID: Yang, Zhihong
Ming, Xiu-Fen
Venue: Frontiers in Immunology
Publisher: Frontiers Media SA
Published: 2014-10-27
Volume: 5
Pages: 533-533
ISSN: 1664-3224 (ISSN-L)
DOI: 10.3389/fimmu.2014.00533
PMC: PMC4209887
OpenAlex: W2018261122
Cited by: 290
References: 107
Citations by year: 2026: 20 · 2025: 31 · 2024: 32 · 2023: 39 · 2022: 30 · 2021: 29 · 2020: 40 · 2019: 23 · 2018: 15 · 2017: 16 · 2016: 5 · 2015: 10
FWCI: 1.01
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
Locations: Frontiers in Immunology (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders: National Science Foundation (120435, 310030)
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (310000-120435/1, 141070, 120435, 310000, 310030)
Schweizerische Herzstiftung
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
Keywords: macrophage polarization, M1/M2 macrophage phenotype, inducible nitric oxide synthase, macrophage inflammation, cardiovascular disease, metabolic disorders, obesity

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

Functions of Arginase Isoforms in Macrophage Inflammatory Responses: Impact on Cardiovascular Diseases and Metabolic Disorders

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks