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  1. Article ; Online: Resolution pharmacology - A fresh approach to the clinical management of human inflammatory diseases.

    Perretti, Mauro / Subramanian, Manikandan

    Seminars in immunology

    2022  Volume 65, Page(s) 101669

    MeSH term(s) Humans ; Inflammation
    Language English
    Publishing date 2022-12-22
    Publishing country England
    Document type Editorial ; Research Support, Non-U.S. Gov't
    ZDB-ID 1018141-6
    ISSN 1096-3618 ; 1044-5323
    ISSN (online) 1096-3618
    ISSN 1044-5323
    DOI 10.1016/j.smim.2022.101669
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    Zs.A 2843: Show issues Location:
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  2. Article ; Online: Tackling inflammation in atherosclerosis: Are we there yet and what lies beyond?

    Bhattacharya, Purbasha / Kanagasooriyan, Ragulan / Subramanian, Manikandan

    Current opinion in pharmacology

    2022  Volume 66, Page(s) 102283

    Abstract: Atherosclerosis is a lipid-driven disease of the artery characterized by chronic non-resolving inflammation. Despite availability of excellent lipid-lowering therapies, atherosclerosis remains the leading cause of disability and death globally. The ... ...

    Abstract Atherosclerosis is a lipid-driven disease of the artery characterized by chronic non-resolving inflammation. Despite availability of excellent lipid-lowering therapies, atherosclerosis remains the leading cause of disability and death globally. The demonstration that suppressing inflammation prevents the adverse clinical manifestations of atherosclerosis in recent clinical trials has led to heightened interest in anti-inflammatory therapies. In this review, we briefly highlight some key anti-inflammatory and pro-resolution pathways, which could be targeted to modulate pathogenesis and stall atherosclerosis progression. We also highlight key challenges that must be overcome to turn the concept of inflammation targeting therapies into clinical reality for atherosclerotic heart disease.
    MeSH term(s) Anti-Inflammatory Agents/therapeutic use ; Atherosclerosis/drug therapy ; Atherosclerosis/metabolism ; Atherosclerosis/pathology ; Coronary Artery Disease ; Humans ; Inflammation/drug therapy ; Inflammation/pathology ; Lipids
    Chemical Substances Anti-Inflammatory Agents ; Lipids
    Language English
    Publishing date 2022-08-28
    Publishing country England
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2037057-X
    ISSN 1471-4973 ; 1471-4892
    ISSN (online) 1471-4973
    ISSN 1471-4892
    DOI 10.1016/j.coph.2022.102283
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    Zs.A 5608: Show issues Location:
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  3. Article ; Online: Hypercholesterolemia promotes autoantibody production and a lupus-like pathology via decreased DNase-mediated clearance of DNA.

    Dhawan, Umesh Kumar / Margraf, Andreas / Lech, Maciej / Subramanian, Manikandan

    Journal of cellular and molecular medicine

    2022  Volume 26, Issue 20, Page(s) 5267–5276

    Abstract: Hypercholesterolemia exacerbates autoimmune response and accelerates the progression of several autoimmune disorders, but the mechanistic basis is not well understood. We recently demonstrated that hypercholesterolemia is associated with increased serum ... ...

    Abstract Hypercholesterolemia exacerbates autoimmune response and accelerates the progression of several autoimmune disorders, but the mechanistic basis is not well understood. We recently demonstrated that hypercholesterolemia is associated with increased serum extracellular DNA levels secondary to a defect in DNase-mediated clearance of DNA. In this study, we tested whether the impaired DNase response plays a causal role in enhancing anti-nuclear antibody levels and renal immune complex deposition in an Apoe
    MeSH term(s) Animals ; Antigen-Antibody Complex ; Autoantibodies ; Autoimmune Diseases ; DNA ; Deoxyribonucleases/metabolism ; Humans ; Hypercholesterolemia/genetics ; Lupus Erythematosus, Systemic ; Mice ; Mice, Knockout, ApoE
    Chemical Substances Antigen-Antibody Complex ; Autoantibodies ; DNA (9007-49-2) ; Deoxyribonucleases (EC 3.1.-)
    Language English
    Publishing date 2022-09-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 2074559-X
    ISSN 1582-4934 ; 1582-4934 ; 1582-1838
    ISSN (online) 1582-4934
    ISSN 1582-4934 ; 1582-1838
    DOI 10.1111/jcmm.17556
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  4. Article ; Online: CD36 pumps fat to defang killer T cells in tumors.

    Subramanian, Manikandan / Marelli-Berg, Federica M

    Cell metabolism

    2021  Volume 33, Issue 8, Page(s) 1509–1511

    Abstract: The tumor microenvironment is immunosuppressive. Here we preview two recent studies from Ma et al. (2021) in Cell Metabolism and Xu et al. (2021) in Immunity that describe a key role of T cell-expressed CD36 in enhancing lipid uptake and mediating lipid ... ...

    Abstract The tumor microenvironment is immunosuppressive. Here we preview two recent studies from Ma et al. (2021) in Cell Metabolism and Xu et al. (2021) in Immunity that describe a key role of T cell-expressed CD36 in enhancing lipid uptake and mediating lipid peroxidation that ultimately leads to CD8+ T cell dysfunction, ferroptosis, and reduced anti-tumor function.
    MeSH term(s) CD36 Antigens ; CD8-Positive T-Lymphocytes ; Ferroptosis ; Humans ; Neoplasms ; Tumor Microenvironment
    Chemical Substances CD36 Antigens
    Language English
    Publishing date 2021-07-31
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 2176834-1
    ISSN 1932-7420 ; 1550-4131
    ISSN (online) 1932-7420
    ISSN 1550-4131
    DOI 10.1016/j.cmet.2021.07.004
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  5. Article ; Online: Dead cell and debris clearance in the atherosclerotic plaque: Mechanisms and therapeutic opportunities to promote inflammation resolution.

    Dhawan, Umesh Kumar / Singhal, Aarushi / Subramanian, Manikandan

    Pharmacological research

    2021  Volume 170, Page(s) 105699

    Abstract: Phagocytic clearance of dead cells and debris is critical for inflammation resolution and maintenance of tissue homeostasis. Consequently, defective clearance of dead cells and debris is associated with initiation and exacerbation of several autoimmune ... ...

    Abstract Phagocytic clearance of dead cells and debris is critical for inflammation resolution and maintenance of tissue homeostasis. Consequently, defective clearance of dead cells and debris is associated with initiation and exacerbation of several autoimmune disorders and chronic inflammatory diseases such as atherosclerosis. The progressive loss of dead cell clearance capacity within the atherosclerotic plaque leads to accumulation of necrotic cells, chronic non-resolving inflammation, and expansion of the necrotic core, which triggers atherosclerotic plaque rupture and clinical manifestation of acute thrombotic cardiovascular adverse events. In this review, we describe the fundamental molecular and cellular mechanisms of dead cell clearance and how it goes awry in atherosclerosis. Finally, we highlight novel therapeutic strategies that enhance dead cell and debris clearance within the atherosclerotic plaque to promote inflammation resolution and atherosclerotic plaque stabilization.
    MeSH term(s) Animals ; Anti-Inflammatory Agents/therapeutic use ; Atherosclerosis/drug therapy ; Atherosclerosis/immunology ; Atherosclerosis/metabolism ; Atherosclerosis/pathology ; Cell Death ; Humans ; Inflammation/drug therapy ; Inflammation/immunology ; Inflammation/metabolism ; Inflammation/pathology ; Macrophages/drug effects ; Macrophages/immunology ; Macrophages/metabolism ; Macrophages/pathology ; Necrosis ; Phagocytosis/drug effects ; Plaque, Atherosclerotic
    Chemical Substances Anti-Inflammatory Agents
    Language English
    Publishing date 2021-06-02
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1003347-6
    ISSN 1096-1186 ; 0031-6989 ; 1043-6618
    ISSN (online) 1096-1186
    ISSN 0031-6989 ; 1043-6618
    DOI 10.1016/j.phrs.2021.105699
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    Zs.A 721: Show issues Location:
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  6. Article: Pomegranate Peel Extract Decreases Plaque Necrosis and Advanced Atherosclerosis Progression in

    Manickam, Vijayprakash / Dhawan, Umesh Kumar / Singh, Damanpreet / Gupta, Mahesh / Subramanian, Manikandan

    Frontiers in pharmacology

    2022  Volume 13, Page(s) 888300

    Abstract: Atherosclerosis is a chronic lipid-driven inflammatory condition of the arteries and is a leading cause of stroke, myocardial infarction, and other peripheral arterial diseases. Plant products rich in polyphenols such as pomegranate juice and peel ... ...

    Abstract Atherosclerosis is a chronic lipid-driven inflammatory condition of the arteries and is a leading cause of stroke, myocardial infarction, and other peripheral arterial diseases. Plant products rich in polyphenols such as pomegranate juice and peel extract are known to have beneficial effects in suppressing atherogenesis. However, the mechanism of action and its effect on advanced atherosclerosis progression which results in adverse clinical outcomes are not well understood. Herein, we use a standardized hydroethanolic extract of
    Language English
    Publishing date 2022-06-01
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2022.888300
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  7. Article ; Online: Colony stimulating factors (CSFs): Complex roles in atherosclerosis.

    Singhal, Aarushi / Subramanian, Manikandan

    Cytokine

    2017  Volume 122, Page(s) 154190

    Abstract: Colony stimulating factors (CSFs) play a central role in the development and functional maturation of immune cells besides having pleiotropic effects on cells of the vascular wall. The production of CSFs is induced by multiple atherogenic and ... ...

    Abstract Colony stimulating factors (CSFs) play a central role in the development and functional maturation of immune cells besides having pleiotropic effects on cells of the vascular wall. The production of CSFs is induced by multiple atherogenic and inflammatory stimuli and their expression levels are often correlated positively with advanced atherosclerotic plaques and adverse cardiovascular events in humans suggesting that CSFs play a critical role in the pathophysiology of atherosclerosis progression. Interestingly, recombinant CSFs as well as anti-CSFs are being increasingly used for diverse clinical indications. However, the effect of these novel therapeutics on atherosclerotic plaque progression is not well understood. Herein, we summarize the currently available literature on the complex role of CSFs in various stages of atherosclerosis and emphasize the necessity for conducting further mechanistic studies in animal models of atherosclerosis as well as the need for evaluating the cardiovascular safety of CSF-based therapies in humans.
    MeSH term(s) Animals ; Atherosclerosis/drug therapy ; Atherosclerosis/metabolism ; Cell Differentiation/drug effects ; Colony-Stimulating Factors/metabolism ; Colony-Stimulating Factors/pharmacology ; Disease Progression ; Granulocyte Colony-Stimulating Factor/metabolism ; Granulocyte Colony-Stimulating Factor/pharmacology ; Granulocyte Colony-Stimulating Factor/therapeutic use ; Humans ; Inflammation/drug therapy ; Inflammation/immunology ; Inflammation/metabolism ; Interleukin-3/metabolism ; Macrophage Colony-Stimulating Factor/metabolism ; Macrophage Colony-Stimulating Factor/pharmacology ; Models, Animal ; Plaque, Atherosclerotic/drug therapy ; Plaque, Atherosclerotic/metabolism
    Chemical Substances Colony-Stimulating Factors ; Interleukin-3 ; Granulocyte Colony-Stimulating Factor (143011-72-7) ; Macrophage Colony-Stimulating Factor (81627-83-0)
    Language English
    Publishing date 2017-11-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1018055-2
    ISSN 1096-0023 ; 1043-4666
    ISSN (online) 1096-0023
    ISSN 1043-4666
    DOI 10.1016/j.cyto.2017.10.012
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    Zs.A 2840: Show issues Location:
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  8. Article ; Online: Hypercholesterolemia Impairs Clearance of Neutrophil Extracellular Traps and Promotes Inflammation and Atherosclerotic Plaque Progression.

    Dhawan, Umesh Kumar / Bhattacharya, Purbasha / Narayanan, Sriram / Manickam, Vijayprakash / Aggarwal, Ayush / Subramanian, Manikandan

    Arteriosclerosis, thrombosis, and vascular biology

    2021  Volume 41, Issue 10, Page(s) 2598–2615

    MeSH term(s) Animals ; Aortic Diseases/etiology ; Aortic Diseases/immunology ; Aortic Diseases/metabolism ; Aortic Diseases/pathology ; Atherosclerosis/etiology ; Atherosclerosis/immunology ; Atherosclerosis/metabolism ; Atherosclerosis/pathology ; Caco-2 Cells ; Deoxyribonuclease I/metabolism ; Disease Models, Animal ; Disease Progression ; Endodeoxyribonucleases/metabolism ; Endoplasmic Reticulum Stress ; Extracellular Traps/metabolism ; Female ; HL-60 Cells ; Hep G2 Cells ; Humans ; Hypercholesterolemia/complications ; Hypercholesterolemia/immunology ; Hypercholesterolemia/metabolism ; Inflammation/etiology ; Inflammation/immunology ; Inflammation/metabolism ; Inflammation Mediators/metabolism ; Male ; Mice, Inbred C57BL ; Mice, Knockout, ApoE ; Necrosis ; Neutrophils/immunology ; Neutrophils/metabolism ; Plaque, Atherosclerotic ; Signal Transduction ; THP-1 Cells ; Mice
    Chemical Substances Inflammation Mediators ; Dnase1l3 protein, mouse (EC 3.1.-) ; Endodeoxyribonucleases (EC 3.1.-) ; Deoxyribonuclease I (EC 3.1.21.1)
    Language English
    Publishing date 2021-08-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1221433-4
    ISSN 1524-4636 ; 1079-5642
    ISSN (online) 1524-4636
    ISSN 1079-5642
    DOI 10.1161/ATVBAHA.120.316389
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    Zs.A 1705: Show issues Location:
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  9. Article ; Online: Efferocytes release extracellular vesicles to resolve inflammation and tissue injury via prosaposin-GPR37 signaling.

    Bhattacharya, Purbasha / Dhawan, Umesh Kumar / Hussain, Mohammed Tayab / Singh, Praveen / Bhagat, Karran Kiran / Singhal, Aarushi / Austin-Williams, Shani / Sengupta, Shantanu / Subramanian, Manikandan

    Cell reports

    2023  Volume 42, Issue 7, Page(s) 112808

    Abstract: Macrophages release soluble mediators following efferocytic clearance of apoptotic cells to facilitate intercellular communication and promote the resolution of inflammation. However, whether inflammation resolution is modulated by extracellular vesicles ...

    Abstract Macrophages release soluble mediators following efferocytic clearance of apoptotic cells to facilitate intercellular communication and promote the resolution of inflammation. However, whether inflammation resolution is modulated by extracellular vesicles (EVs) and vesicular mediators released by efferocytes is not known. We report that efferocyte-derived EVs express prosaposin, which binds to macrophage GPR37 to increase expression of the efferocytosis receptor Tim4 via an ERK-AP1-dependent signaling axis, leading to increased macrophage efferocytosis efficiency and accelerated resolution of inflammation. Neutralization and knockdown of prosaposin or blocking GRP37 abrogates the pro-resolution effects of efferocyte-derived EVs in vivo. Administration of efferocyte-derived EVs in a murine model of atherosclerosis is associated with an increase in lesional macrophage efferocytosis efficiency and a decrease in plaque necrosis and lesional inflammation. Thus, we establish a critical role for efferocyte-derived vesicular mediators in increasing macrophage efferocytosis efficiency and accelerating the resolution of inflammation and tissue injury.
    MeSH term(s) Animals ; Mice ; Apoptosis ; Extracellular Vesicles/metabolism ; Inflammation/metabolism ; Macrophages/metabolism ; Phagocytosis ; Saposins/metabolism ; Receptors, G-Protein-Coupled/metabolism
    Chemical Substances Saposins ; Gpr37 protein, mouse ; Receptors, G-Protein-Coupled ; Psap protein, mouse
    Language English
    Publishing date 2023-07-11
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2023.112808
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: A new RIDDle in DC-mediated cross-presentation.

    Subramanian, Manikandan / Tabas, Ira

    Nature immunology

    2014  Volume 15, Issue 3, Page(s) 213–215

    MeSH term(s) Animals ; Cross-Priming/immunology ; DNA-Binding Proteins/immunology ; Dendritic Cells/immunology ; Endoribonucleases/immunology ; Protein Unfolding ; Protein-Serine-Threonine Kinases/immunology ; Regulatory Factor X Transcription Factors ; Transcription Factors/immunology ; Unfolded Protein Response/immunology
    Chemical Substances DNA-Binding Proteins ; Regulatory Factor X Transcription Factors ; Transcription Factors ; Ern1 protein, mouse (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; Endoribonucleases (EC 3.1.-)
    Language English
    Publishing date 2014-02-19
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/ni.2826
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