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Functions of Arginase Isoforms in Macrophage Inflammatory Responses: Impact on Cardiovascular Diseases and Metabolic Disorders
Open accessAbstract
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.
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“ARG1 in myeloid cells mainly functions as an enzyme to hydrolyze arginine to produce ornithine as part of the urea cycle, which both promotes tissue repair through generation of polyamines and collagens, and also reduces nitric oxide production from inducible nitric oxide synthase through decreasing intracellular arginine availability (76–78).”
From Trem2 promotes anti-inflammatory responses in microglia and is suppressed under pro-inflammatory conditions (2020) · cites this paper as [76]
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“ornithine that assists cell proliferation and repair of damaged tissue [29].”
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“…synthase (iNOS) and arginase are enzymes that are widely used as the markers for macrophage phenotype (M1/M2) characterization (Mills, 2012; Yang & Ming, 2014). iNOS metabolizes the amino acid arginine to produce nitric oxide which inhibits cell proliferation while arginase metabolizes Arginine…”
BackgroundArginase Pathway in Acute Retina and Brain Injury: Therapeutic Opportunities and Unexplored Avenues
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“Specifically, use of A1 as a therapy for acute CNS ischemia and AD is an appealing approach since PEG-A1 is already being clinically tested in patients with advanced hepatocellular carcinoma and melanoma, and it appears to be safe and well-tolerated (Yau et al., 2013, 2015; De Santo et al., 2018).”
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“Therefore, macrophages are an important therapeutic target in the treatment of pathological states associated with chronic inflammation (e.g., autoimmune and cardiovascular diseases) (Bronte and Zanovello, 2005; Cathcart, 2004; Cohen, 2002; Yang and Ming, 2014).”
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Metabolic Reprogramming of Mouse Bone Marrow Derived Macrophages Following Erythrophagocytosis
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“By contrast, alternatively activated (M2) macrophages are typically less migratory owning to their extensive roles in repairing tissuedamage, and have a proresolution profile characterized by the secretion of cytokines, such as transforming growth factor-β (TGF-β), IL-4, IL-10, and IL-13 (Zhang and An, 2007; Nahrendor…”
BackgroundTelocytes regulate macrophages in periodontal disease
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Is the Arginase Pathway a Novel Therapeutic Avenue for Diabetic Retinopathy?
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“On the other hand, the A2 isoform has been suggested to be present in pro-inflammatory M1-like macrophage [100].”
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“These findings contrast with prior literature arguing that Arg1 is a marker of the M2 macrophage phenotype 55–57 .”
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Metadata
- Authors
- Yang, Z., & Ming, X.-F.
- Affiliations
- University of Fribourg (CH)
- Corresponding author
- 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)
- 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
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