The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Arginase regulates red blood cell nitric oxide synthase and export of cardioprotective nitric oxide bioactivity
Open accessAbstract
Significance: Nitric oxide from endothelial cells is important for regulating cardiovascular function. Recent data suggest that red blood cells are a source for nitric oxide. We examined the function of red blood cell nitric oxide and the regulation of its formation by the enzyme arginase. We show that red blood cells contain arginase that inhibits nitric oxide export. The function was tested in a heart model subjected to ischemia. The recovery of heart function after ischemia was improved following inhibition of red blood cell arginase. This effect depended on the specific protein producing nitric oxide. The results demonstrate an important function by red blood cells in regulating heart function during ischemia via nitric oxide production under tight control by arginase.
Overview
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
Cites
Statistics
Verification
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?
In the citing paper
“The selectivity is partly due to a lack of structural resemblance with purines; this also reduces side effects of purine and pyrimidine metabolism (1041).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [1041]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The L-Arginine-Nitric Oxide Pathway
Epstein, F. H., Moncada, S., & Higgs, A. (1993) · New England Journal of Medicine · doi:10.1056/nejm199312303292706 · Cited by 6,678
Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation
Cosby, K., Partovi, K. S., Crawford, J. H., Patel, R. P., Reiter, C. D., Martyr, S., Yang, B. K., Waclawiw, M. A., Zalos, G., Xu, X., et al. (2003) · Nature Medicine · doi:10.1038/nm954 · Cited by 1,807
S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control
Jia, L., Bonaventura, C., Bonaventura, J., & Stamler, J. S. (1996) · Nature · doi:10.1038/380221a0 · Cited by 1,592
Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver
Duranski, M. R., Greer, J. J. M., Dejam, A., Jaganmohan, S., Hogg, N., Langston, W., Patel, R. P., Yet, S.-F., Wang, X., Kevil, C. G., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci22493 · Cited by 674
Evolution of adverse changes in stored RBCs
Bennett‐Guerrero, E., Veldman, T. H., Doctor, A., Telen, M. J., Ortel, T. L., Reid, T. S., Mulherin, M. A., Zhu, H., Buck, R. D., Califf, R. M., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0708160104 · Cited by 614
Webb, A., Bond, R., McLean, P., Uppal, R., Benjamin, N., & Ahluwalia, A. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0402927101 · Cited by 608 · cited 1×
“Nitrite may also be involved because it has been shown to be reduced to NO in the ischemic myocardium and to protect against ischemia-reperfusion injury (2, 4).”
BackgroundARGINASE: A CRITICAL REGULATOR OF NITRIC OXIDE SYNTHESIS AND VASCULAR FUNCTION
Durante, W., Johnson, F. K., & Johnson, R. A. (2007) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2007.04638.x · Cited by 577 · cited 11×
“After the washing step, the same volume of L-arginine-containing KH buffer was added to the RBCs and gently mixed and incubated with nor-NOHA (0.1–1 mM) at 37 °C for 30 min.”
BackgroundInfluentialRed blood cells express a functional endothelial nitric oxide synthase
Kleinbongard, P. (2005) · Blood · doi:10.1182/blood-2005-10-3992 · Cited by 575
Berkowitz, D. E., White, R., Li, D., Minhas, K. M., Cernetich, A., Kim, S., Burke, S., Shoukas, A. A., Nyhan, D., Champion, H. C., et al. (2003) · Circulation · doi:10.1161/01.cir.0000092948.04444.c7 · Cited by 486
Heusch, G., Boengler, K., & Schulz, R. (2008) · Circulation · doi:10.1161/circulationaha.108.805242 · Cited by 435
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–147 of 147
Başarıcı, İ., Özen, N., Kilavuz, E., Kısak, F., Basralı, F., Yaraş, N., Köksoy, S., Çelik, M. L., & Ülker, P. (2020) · Clinical Hemorheology and Microcirculation · doi:10.3233/ch-200892 · Cited by 10
Regulatory effects of resveratrol on nitric oxide signaling in cardiovascular diseases
Abolfazli, S., Karav, S., Johnston, T. P., & Sahebkar, A. (2025) · Pharmacological Reports · doi:10.1007/s43440-025-00694-w · Cited by 9
RBC-GEM: A genome-scale metabolic model for systems biology of the human red blood cell
Haiman, Z. B., Key, A., D’Alessandro, A., & Palsson, B. Ø. (2025) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1012109 · Cited by 14
Endothelium Seeing Red: Should We Redefine eNOS as the Endothelial and Erythrocytic NOS?
Gladwin, M. T. (2021) · Circulation · doi:10.1161/circulationaha.121.055679 · Cited by 9
Erythrocytes and cardiovascular complications
Zhou, Z., Yang, J., & Pernow, J. (2018) · Aging · doi:10.18632/aging.101688 · Cited by 7
Self-citationChu, Y., Lu, C., Lin, T., Tsou, M., Hsu, Y., Ho, S., Tung, C., Tseng, C., Li, M., & Lee, H. (2016) · American Journal of Hypertension · doi:10.1093/ajh/hpw161 · Cited by 6
de Castro, A. L., Fernandes, R. O., Ortiz, V. D., Carraro, C. C., Bonetto, J. H. P., Fernandes, T. R. G., Conzatti, A., Siqueira, R., Tavares, Â. M. V., Belló‐Klein, A., et al. (2020) · Archives of Physiology and Biochemistry · doi:10.1080/13813455.2020.1779752 · Cited by 6
Muessig, J. M., Kaya, S., Moellhoff, L., Noelle, J., Pareja, L. H., Masyuk, M., Gerdes, N., Pernow, J., Kelm, M., & Jung, C. (2019) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/1074248419874348 · Cited by 6
Self-citationRed Blood Cells Deserve Attention in Patients With Type 2 Diabetes
Vilahur, G. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.05.053 · Cited by 6
Heuser, S. K., Li, J., Li, Z., LoBue, A., Heard, K., Hocks, J., Suvorava, T., Cadeddu, R., Strupp, C., Dunaway, L. S., et al. (2025) · Redox Biology · doi:10.1016/j.redox.2025.103768 · Cited by 5
Self-citationKutikhin, A. G. (2021) · Fundamental and Clinical Medicine · doi:10.23946/2500-0764-2021-6-1-82-102 · Cited by 5
Mochol, J., Gawryś, J., Szahidewicz-Krupska, E., Wiśniewski, J. Ł., Fortuna, P., Rola, P., Martynowicz, H., & Doroszko, A. (2022) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph192214719 · Cited by 5
Tengbom, J., Kontidou, E., Collado, A., Yang, J., Alvarsson, M., Brinck, J. W., Rössner, S. M., Zhou, Z., Pernow, J., & Mahdi, A. (2024) · Clinical Science · doi:10.1042/cs20240447 · Cited by 5
Self-citationPudewell, S., Lissy, J., Nakhaeizadeh, H., Taha, M. S., Akbarzadeh, M., Adariani, S. R., Nakhaei‐Rad, S., Li, J., Kordes, C., Häussinger, D., et al. (2022) · Cells · doi:10.3390/cells11030508 · Cited by 5
Cortese-Krott, M. M., Kramer, C. M., & Kelm, M. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804273-1.00014-4 · Cited by 5
Rho-kinase is a negative regulator of red blood cell eNOS under basal conditions
Ülker, P., Özen, N., Abduleyeva, G., Köksoy, S., Yaraş, N., & Basralı, F. (2019) · Clinical Hemorheology and Microcirculation · doi:10.3233/ch-190578 · Cited by 5
RBC-GEM: a Knowledge Base for Systems Biology of Human Red Blood Cell MetabolismPreprint
Haiman, Z. B., D’Alessandro, A., & Palsson, B. Ø. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.04.26.591249 · Cited by 5
Tengbom, J., Humoud, R., Kontidou, E., Jiao, T., Yang, J., Hedin, U., Zhou, Z., Jurga, J., Collado, A., Mahdi, A., et al. (2024) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00443.2024 · Cited by 4
Self-citationRao, S., Zhang, J., Lin, J., Wan, J., & Chen, Y. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11247373 · Cited by 4
Red Blood Cells in Normal and Pathological States: Redox Reactions of Hemoglobin
Gwoździński, K., Pieniążek, A., & Gwoździński, Ł. (2026) · Molecules · doi:10.3390/molecules31030444 · Cited by 3
The functional insight into the genetics of cardiovascular disease: results from the post-GWAS study
Bryzgalov, L. O., Korbolina, E. E., Damarov, I. S., & Merkulova, T. I. (2022) · Vavilov Journal of Genetics and Breeding · doi:10.18699/vjgb-22-10 · Cited by 3
Muessig, J. M., Moellhoff, L., Noelle, J., Kaya, S., Pareja, L. H., Masyuk, M., Roden, M., Kelm, M., & Jung, C. (2020) · Nitric Oxide · doi:10.1016/j.niox.2020.01.008 · Cited by 3
Değirmençay, Ş., Küçükler, S., Özdemir, S., & Kaman, R. (2022) · Veterinary Parasitology · doi:10.1016/j.vetpar.2022.109855 · Cited by 2
Stoian, I. A.-M., Iosif, L., Gîlcă, M., Vlad, A., Tivig, I. C., Bradescu, O. M., & Savu, O. (2024) · Life · doi:10.3390/life14050556 · Cited by 2
Cortese-Krott, M. M., & Kelm, M. (2015) · Redox Biology · doi:10.1016/j.redox.2015.08.004 · Cited by 2
Kontidou, E., Humoud, R., Chernogubova, E., Alvarsson, M., Mäegdefessel, L., Collado, A., Pernow, J., & Zhou, Z. (2024) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00609.2024 · Cited by 1
Self-citationThe Erythrocyte–ROS Axis in Thrombosis and Hemostasis
Borghi, S., Nencini, F., Giurranna, E., Fiorillo, C., & Becatti, M. (2025) · Seminars in Thrombosis and Hemostasis · doi:10.1055/a-2615-0136 · Cited by 1
Kontidou, E., Collado, A., Humoud, R., Manickam, K., Tengbom, J., Jiao, T., Alvarsson, M., Yang, J., Mellbin, L., Mahdi, A., et al. (2026) · Diabetes · doi:10.2337/db25-0463 · Cited by 1
Self-citationChronic Erythrocyte NO Production Accelerates Atherosclerosis by Increasing SMC De Novo Lipogenesis
Sun, B., Gogiraju, R., Greulich, F., Kumi, F., Ghasemi, I., Bochenek, M. L., Pagel, S., van der Vorst, E. P. C., Khuu, M. P., Moiko, K., et al. (2026) · Circulation Research · doi:10.1161/circresaha.125.327866 · Cited by 1
Modulators of Nitric Oxide-Dependent Osteoinductive Activity of Human Red Blood Cells
Pavlaki, M., Moiko, K., Thomaidis, A., Chalikias, G., Schäfer, K., Konstantinides, S., & Tziakas, D. N. (2022) · TH Open · doi:10.1055/a-1877-9870 · Cited by 1
Inducible nitric oxide synthase 2 (NOS2) and antitumor γδ-T cells
Leyva, B. K., & Bonavida, B. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-13342-8.00007-7 · Cited by 1
A Review on Erectile Dysfunction Among Hypertensive Patients on Pharmacotherapy
Boamah, B. B. (2017) · International Journal of Clinical and Experimental Medical Sciences · doi:10.11648/j.ijcems.20170306.15 · Cited by 1
Mechanotransduction and Vascular Resistance
Thiriet, M. (2015) · Springer eBooks · doi:10.1007/978-3-642-37078-6_258
Guo, J., Zhang, A., Zheng, D., Jiang, C., Zheng, Z., & Li, Z. (2015) · Journal of Histotechnology · doi:10.1179/2046023615y.0000000008
Tsikas, D. (2015) · Redox Biology · doi:10.1016/j.redox.2015.01.019
RetractedErythrocytes Induce Vascular Dysfunction in COVID-19Preprint
Mahdi, A., Collado, A., Tengbom, J., Jiao, T., Wodaje, T., Johanssson, N., Farnebo, F. A., Färnert, A., Yang, J., Lundberg, J. O., et al. (2021) · SSRN Electronic Journal · doi:10.2139/ssrn.3945298
Self-citationMechanotransduction and Vascular Resistance
Thiriet, M. (2014) · Springer eBooks · doi:10.1007/978-3-642-37393-0_258-2
Mechanotransduction and Vascular Resistance
Thiriet, M. (2014) · Springer eBooks · doi:10.1007/978-3-642-37393-0_258-1
Tsikas, D. (2015) · Redox Biology · doi:10.1016/j.redox.2015.01.020
RetractedA High-Throughput Colorimetric Microplate Assay for Determination of Plasma Arginase Activity
Smith, N. J., Maddahfar, M., Gunasegaran, B., McGuire, H. M., & Groth, B. F. D. S. (2023) · Methods in molecular biology · doi:10.1007/978-1-0716-2942-0_29
Butun, T. T., Özen, N., Öztürk, N., Yildirim, A. Ö., Kilavuz, E., Karadağ, C., Yüksel, B. A., Basralı, F., Karadağ, B., & Ülker, P. (2024) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365513.2024.2394982
Sickle Cell Trait and Vascular Health: Insights into Complications and Management
Soni, Z., Maheta, D., Agrawal, S. P., Frishman, W. H., & Aronow, W. S. (2025) · Cardiology in Review · doi:10.1097/crd.0000000000000857
Gogiraju, R., Sun, B., Bochenek, M. L., Wittig, I., Rezende, F., Lopez, M., Wirth, A., Zhao, W., Böhm, E. W., Guliani, P., et al. (2026) · Redox Biology · doi:10.1016/j.redox.2026.104201
The Ugly Side of NO: Erythrocyte-Derived NO and Atherosclerosis
Hill, B. G. (2026) · Circulation Research · doi:10.1161/circresaha.126.328845
Gupta, N., Mehra, T., Srivastava, A., & Mishra, A. K. (2026) · Journal of Plant Physiology · doi:10.1016/j.jplph.2026.154831
Peysakhova, L., Chrysopoulou, M., & Rinschen, M. M. (2026) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2026.09.005
Metadata
- Authors
- Yang, J., Gonon, A. T., Sjöquist, P.-O., Lundberg, J. O., & Pernow, J.
- Affiliations
- Karolinska University Hospital (SE)
- Divison of Cardiology, Department of Medicine, and
- Karolinska Institutet (SE)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-08-26
- Volume
- 110
- Issue
- 37
- Pages
- 15049-15054
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3773799
- OpenAlex
- W2134566930
- Cited by
- 147
- References
- 38
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 11 · 2023: 9 · 2022: 15 · 2021: 16 · 2020: 11 · 2019: 15 · 2018: 13 · 2017: 10 · 2016: 7 · 2015: 16 · 2014: 9 · 2013: 2
- FWCI
- 7.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
- Keywords
- arginase-1, endothelial nitric oxide synthase, erythrocytes, nitric oxide, myocardial ischemia-reperfusion injury, cardioprotection, eNOS knockout mice
- MeSH terms
- Animals, Arginase, Arginine, Biological Transport, Active, Cardiotonic Agents, Enzyme Inhibitors, Erythrocytes, Humans, Mice, Inbred C57BL, Nitrates, Nitric Oxide, Nitrites, Myocardial Reperfusion Injury, Rats, Wistar, Mice, Knockout, Mice, Rats, Nitric Oxide Synthase Type III
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
