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  1. Article ; Online: Targeting PAR4 to Reduce Atherosclerosis.

    Barrett, Tessa J

    Arteriosclerosis, thrombosis, and vascular biology

    2023  Volume 43, Issue 11, Page(s) 2179–2182

    MeSH term(s) Mice ; Animals ; Mice, Knockout ; Coronary Vessels ; Receptors, Thrombin ; Receptor, PAR-1 ; Atherosclerosis/prevention & control ; Fibrosis
    Chemical Substances Receptors, Thrombin ; Receptor, PAR-1
    Language English
    Publishing date 2023-09-28
    Publishing country United States
    Document type Editorial ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 1221433-4
    ISSN 1524-4636 ; 1079-5642
    ISSN (online) 1524-4636
    ISSN 1079-5642
    DOI 10.1161/ATVBAHA.123.320046
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Platelet-monocyte aggregates: molecular mediators of thromboinflammation.

    Rolling, Christina C / Barrett, Tessa J / Berger, Jeffrey S

    Frontiers in cardiovascular medicine

    2023  Volume 10, Page(s) 960398

    Abstract: Platelets, key facilitators of primary hemostasis and thrombosis, have emerged as crucial cellular mediators of innate immunity and inflammation. Exemplified by their ability to alter the phenotype and function of monocytes, activated platelets bind to ... ...

    Abstract Platelets, key facilitators of primary hemostasis and thrombosis, have emerged as crucial cellular mediators of innate immunity and inflammation. Exemplified by their ability to alter the phenotype and function of monocytes, activated platelets bind to circulating monocytes to form monocyte-platelet aggregates (MPA). The platelet-monocyte axis has emerged as a key mechanism connecting thrombosis and inflammation. MPA are elevated across the spectrum of inflammatory and autoimmune disorders, including cardiovascular disease, systemic lupus erythematosus (SLE), and COVID-19, and are positively associated with disease severity. These clinical disorders are all characterized by an increased risk of thromboembolic complications. Intriguingly, monocytes in contact with platelets become proinflammatory and procoagulant, highlighting that this interaction is a central element of thromboinflammation.
    Language English
    Publishing date 2023-05-15
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2781496-8
    ISSN 2297-055X
    ISSN 2297-055X
    DOI 10.3389/fcvm.2023.960398
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Macrophages in Atherosclerosis Regression.

    Barrett, Tessa J

    Arteriosclerosis, thrombosis, and vascular biology

    2019  Volume 40, Issue 1, Page(s) 20–33

    Abstract: Macrophages play a central role in the development of atherosclerotic cardiovascular disease (ASCVD), which encompasses coronary artery disease, peripheral artery disease, cerebrovascular disease, and aortic atherosclerosis. In each vascular bed, ... ...

    Abstract Macrophages play a central role in the development of atherosclerotic cardiovascular disease (ASCVD), which encompasses coronary artery disease, peripheral artery disease, cerebrovascular disease, and aortic atherosclerosis. In each vascular bed, macrophages contribute to the maintenance of the local inflammatory response, propagate plaque development, and promote thrombosis. These central roles, coupled with their plasticity, makes macrophages attractive therapeutic targets in stemming the development of and stabilizing existing atherosclerosis. In the context of ASCVD, classically activated M1 macrophages initiate and sustain inflammation, and alternatively activated M2 macrophages resolve inflammation. However, this classification is now considered an oversimplification, and a greater understanding of plaque macrophage physiology in ASCVD is required to aid in the development of therapeutics to promote ASCVD regression. Reviewed herein are the macrophage phenotypes and molecular regulators characteristic of ASCVD regression, and the current murine models of ASCVD regression.
    MeSH term(s) Animals ; Atherosclerosis/immunology ; Atherosclerosis/metabolism ; Atherosclerosis/pathology ; Coronary Artery Disease/immunology ; Coronary Artery Disease/metabolism ; Coronary Artery Disease/pathology ; Disease Progression ; Humans ; Leukocyte Count ; Macrophage Activation ; Macrophages/metabolism ; Macrophages/microbiology ; Macrophages/pathology ; Phenotype ; Plaque, Atherosclerotic/immunology ; Plaque, Atherosclerotic/metabolism ; Plaque, Atherosclerotic/pathology
    Language English
    Publishing date 2019-11-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1221433-4
    ISSN 1524-4636 ; 1079-5642
    ISSN (online) 1524-4636
    ISSN 1079-5642
    DOI 10.1161/ATVBAHA.119.312802
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Aspirin for the Primary Prevention of Cardiovascular Disease: Time for a Platelet-Guided Approach.

    Cofer, Lucas B / Barrett, Tessa J / Berger, Jeffrey S

    Arteriosclerosis, thrombosis, and vascular biology

    2022  Volume 42, Issue 10, Page(s) 1207–1216

    Abstract: Aspirin protects against atherothrombosis while increasing the risk of major bleeding. Although it is widely used to prevent cardiovascular disease (CVD), its benefit does not outweigh its risk for primary CVD prevention in large population settings. The ...

    Abstract Aspirin protects against atherothrombosis while increasing the risk of major bleeding. Although it is widely used to prevent cardiovascular disease (CVD), its benefit does not outweigh its risk for primary CVD prevention in large population settings. The recent United States Preventive Services Task Force guidelines on aspirin use to prevent CVD reflect this clinical tradeoff as well as the persistent struggle to define a population that would benefit from prophylactic aspirin therapy. Past clinical trials of primary CVD prevention with aspirin have not included consideration of a biomarker relevant to aspirin's mechanism of action, platelet inhibition. This approach is at odds with the paradigm used in other key areas of pharmacological CVD prevention, including antihypertensive and statin therapy, which combine cardiovascular risk assessment with the measurement of mechanistic biomarkers (eg, blood pressure and LDL [low-density lipoprotein]-cholesterol). Reliable methods for quantifying platelet activity, including light transmission aggregometry and platelet transcriptomics, exist and should be considered to identify individuals at elevated cardiovascular risk due to a hyperreactive platelet phenotype. Therefore, we propose a new, platelet-guided approach to the study of prophylactic aspirin therapy. We think that this new approach will reveal a population with hyperreactive platelets who will benefit most from primary CVD prevention with aspirin and usher in a new era of precision-guided antiplatelet therapy.
    MeSH term(s) Antihypertensive Agents/therapeutic use ; Aspirin/therapeutic use ; Cardiovascular Diseases/epidemiology ; Cholesterol ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Lipoproteins, LDL ; Platelet Aggregation Inhibitors/adverse effects ; Primary Prevention/methods
    Chemical Substances Antihypertensive Agents ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Lipoproteins, LDL ; Platelet Aggregation Inhibitors ; Cholesterol (97C5T2UQ7J) ; Aspirin (R16CO5Y76E)
    Language English
    Publishing date 2022-09-01
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1221433-4
    ISSN 1524-4636 ; 1079-5642
    ISSN (online) 1524-4636
    ISSN 1079-5642
    DOI 10.1161/ATVBAHA.122.318020
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Coronary Microvascular Dysfunction Is Associated With a Proinflammatory Circulating Transcriptome in Patients With Nonobstructive Coronary Arteries.

    Smilowitz, Nathaniel R / Schlamp, Florencia / Hausvater, Anaïs / Joa, Amanda / Serrano-Gomez, Claudia / Farid, Ayman / Hochman, Judith S / Barrett, Tessa J / Reynolds, Harmony R / Berger, Jeffrey S

    Arteriosclerosis, thrombosis, and vascular biology

    2024  Volume 44, Issue 4, Page(s) 997–999

    MeSH term(s) Humans ; Coronary Vessels ; Transcriptome ; Myocardial Ischemia ; Coronary Artery Disease/genetics ; Coronary Angiography ; Microcirculation ; Coronary Circulation
    Language English
    Publishing date 2024-02-01
    Publishing country United States
    Document type Letter
    ZDB-ID 1221433-4
    ISSN 1524-4636 ; 1079-5642
    ISSN (online) 1524-4636
    ISSN 1079-5642
    DOI 10.1161/ATVBAHA.123.320471
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Monocytes and macrophages in atherogenesis.

    Amengual, Jaume / Barrett, Tessa J

    Current opinion in lipidology

    2019  Volume 30, Issue 5, Page(s) 401–408

    Abstract: Purpose of review: Monocytes and macrophages are key players in the pathogenesis of atherosclerosis and dictate atherogenesis growth and stability. The heterogeneous nature of myeloid cells concerning their metabolic and phenotypic function is ... ...

    Abstract Purpose of review: Monocytes and macrophages are key players in the pathogenesis of atherosclerosis and dictate atherogenesis growth and stability. The heterogeneous nature of myeloid cells concerning their metabolic and phenotypic function is increasingly appreciated. This review summarizes the recent monocyte and macrophage literature and highlights how differing subsets contribute to atherogenesis.
    Recent findings: Monocytes are short-lived cells generated in the bone marrow and released to circulation where they can produce inflammatory cytokines and, importantly, differentiate into long-lived macrophages. In the context of cardiovascular disease, a myriad of subtypes, exist with each differentially contributing to plaque development. Herein we describe recent novel characterizations of monocyte and macrophage subtypes and summarize the recent literature on mediators of myelopoiesis.
    Summary: An increased understanding of monocyte and macrophage phenotype and their molecular regulators is likely to translate to the development of new therapeutic targets to either stem the growth of existing plaques or promote plaque stabilization.
    MeSH term(s) Atherosclerosis/genetics ; Atherosclerosis/immunology ; Bone Marrow Cells/immunology ; Cell Differentiation/immunology ; Cytokines/metabolism ; Humans ; Macrophages/cytology ; Macrophages/immunology ; Monocytes/cytology ; Monocytes/immunology ; Myelopoiesis/genetics ; Plaque, Atherosclerotic/genetics ; Plaque, Atherosclerotic/immunology
    Chemical Substances Cytokines
    Language English
    Publishing date 2019-10-31
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1045394-5
    ISSN 1473-6535 ; 0957-9672
    ISSN (online) 1473-6535
    ISSN 0957-9672
    DOI 10.1097/MOL.0000000000000634
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Platelet inhibition by low-dose aspirin is not influenced by body mass or weight.

    Heffron, Sean P / Windheim, Joseph / Barrett, Tessa J / Voora, Deepak / Berger, Jeffrey S

    Platelets

    2022  Volume 33, Issue 8, Page(s) 1208–1213

    Abstract: Aspirin's clinical efficacy may be influenced by body weight and mass. Although inadequate platelet inhibition by aspirin is suggested as responsible, evidence for this in non-diabetic patients is sparse. We investigated the influence of body weight and ... ...

    Abstract Aspirin's clinical efficacy may be influenced by body weight and mass. Although inadequate platelet inhibition by aspirin is suggested as responsible, evidence for this in non-diabetic patients is sparse. We investigated the influence of body weight and mass on aspirin's inhibition of platelet aggregation in healthy adults without diabetes. Cohort one (NYU, n = 84) had light transmission aggregometry (LTA) of platelet-rich plasma to submaximal adenosine diphosphate (ADP) and arachidonic acid (AA) before and following 1 week of daily 81 mg non-enteric coated aspirin. Subjects in the validation cohort (Duke, n = 66) were randomized to 81 mg or 325 mg non-enteric coated aspirin for 4 weeks, immediately followed by 4 weeks of the other dose, with LTA to submaximal collagen, ADP, and AA before and after each dosage period. Body mass index (BMI) range was 18.0-57.5 kg/m
    MeSH term(s) Adenosine Diphosphate/pharmacology ; Adult ; Arachidonic Acid/pharmacology ; Aspirin/pharmacology ; Aspirin/therapeutic use ; Blood Platelets ; Body Weight ; Collagen/pharmacology ; Humans ; Platelet Aggregation ; Platelet Aggregation Inhibitors/pharmacology ; Platelet Aggregation Inhibitors/therapeutic use ; Platelet Function Tests
    Chemical Substances Platelet Aggregation Inhibitors ; Arachidonic Acid (27YG812J1I) ; Adenosine Diphosphate (61D2G4IYVH) ; Collagen (9007-34-5) ; Aspirin (R16CO5Y76E)
    Language English
    Publishing date 2022-06-29
    Publishing country England
    Document type Journal Article ; Randomized Controlled Trial
    ZDB-ID 1034283-7
    ISSN 1369-1635 ; 0953-7104
    ISSN (online) 1369-1635
    ISSN 0953-7104
    DOI 10.1080/09537104.2022.2087868
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: HDL and Reverse Cholesterol Transport.

    Ouimet, Mireille / Barrett, Tessa J / Fisher, Edward A

    Circulation research

    2019  Volume 124, Issue 10, Page(s) 1505–1518

    Abstract: Cardiovascular disease, with atherosclerosis as the major underlying factor, remains the leading cause of death worldwide. It is well established that cholesterol ester-enriched foam cells are the hallmark of atherosclerotic plaques. Multiple lines of ... ...

    Abstract Cardiovascular disease, with atherosclerosis as the major underlying factor, remains the leading cause of death worldwide. It is well established that cholesterol ester-enriched foam cells are the hallmark of atherosclerotic plaques. Multiple lines of evidence support that enhancing foam cell cholesterol efflux by HDL (high-density lipoprotein) particles, the first step of reverse cholesterol transport (RCT), is a promising antiatherogenic strategy. Yet, excitement towards the therapeutic potential of manipulating RCT for the treatment of cardiovascular disease has faded because of the lack of the association between cardiovascular disease risk and what was typically measured in intervention trials, namely HDL cholesterol, which has an inconsistent relationship to HDL function and RCT. In this review, we will summarize some of the potential reasons for this inconsistency, update the mechanisms of RCT, and highlight conditions in which impaired HDL function or RCT contributes to vascular disease. On balance, the evidence still argues for further research to better understand how HDL functionality contributes to RCT to develop prevention and treatment strategies to reduce the risk of cardiovascular disease.
    MeSH term(s) ATP Binding Cassette Transporter 1/metabolism ; ATP Binding Cassette Transporter, Subfamily G, Member 1/metabolism ; Atherosclerosis/etiology ; Atherosclerosis/metabolism ; Atherosclerosis/therapy ; Autophagy/physiology ; Biological Transport ; Cardiovascular Diseases/etiology ; Cardiovascular Diseases/metabolism ; Cardiovascular Diseases/therapy ; Cholesterol/metabolism ; Diabetes Mellitus/metabolism ; Foam Cells/metabolism ; Humans ; Lipoproteins, HDL/metabolism ; Lymphatic Vessels/metabolism ; Muscle, Smooth, Vascular/cytology ; Plaque, Atherosclerotic/pathology
    Chemical Substances ABCA1 protein, human ; ABCG1 protein, human ; ATP Binding Cassette Transporter 1 ; ATP Binding Cassette Transporter, Subfamily G, Member 1 ; Lipoproteins, HDL ; Cholesterol (97C5T2UQ7J)
    Language English
    Publishing date 2019-05-08
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
    ZDB-ID 80100-8
    ISSN 1524-4571 ; 0009-7330 ; 0931-6876
    ISSN (online) 1524-4571
    ISSN 0009-7330 ; 0931-6876
    DOI 10.1161/CIRCRESAHA.119.312617
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Platelet LGALS3BP as a Mediator of Myeloid Inflammation in Systemic Lupus Erythematosus.

    El Bannoudi, Hanane / Cornwell, MacIntosh / Luttrell-Williams, Elliot / Engel, Alexis / Rolling, Christina / Barrett, Tessa J / Izmirly, Peter / Belmont, H Michael / Ruggles, Kelly / Clancy, Robert / Buyon, Jill / Berger, Jeffrey S

    Arthritis & rheumatology (Hoboken, N.J.)

    2023  Volume 75, Issue 5, Page(s) 711–722

    Abstract: Objective: Platelets are mediators of inflammation with immune effector cell properties and have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). This study investigated the role of platelet-associated lectin, galactoside- ... ...

    Abstract Objective: Platelets are mediators of inflammation with immune effector cell properties and have been implicated in the pathogenesis of systemic lupus erythematosus (SLE). This study investigated the role of platelet-associated lectin, galactoside-binding, soluble 3 binding protein (LGALS3BP) as a mediator of inflammation in SLE and as a potential biomarker associated with clinical phenotypes.
    Methods: We performed RNA sequencing on platelets from patients with SLE (n = 54) and on platelets from age-, sex-, and race/ethnicity-matched healthy controls (n = 18) and measured LGALS3BP levels in platelet releasate and in circulating serum. We investigated the association between LGALS3BP levels and the prevalence, disease severity, and clinical phenotypes of SLE and studied platelet-mediated effects on myeloid inflammation.
    Results: Platelets from patients with SLE exhibited increased expression of LGALS3BP (fold change 4.0, adjusted P = 6.02 × 10
    Conclusions: Our results support that platelets act as potent effector cells that contribute to the pathogenesis of SLE by secreting proinflammatory LGALS3BP, which also represents a novel biomarker of SLE clinical activity.
    MeSH term(s) Humans ; Blood Platelets/metabolism ; Carrier Proteins/metabolism ; Lupus Erythematosus, Systemic ; Inflammation/metabolism ; Biomarkers ; Antigens, Neoplasm/metabolism ; Biomarkers, Tumor
    Chemical Substances Carrier Proteins ; Biomarkers ; LGALS3BP protein, human ; Antigens, Neoplasm ; Biomarkers, Tumor
    Language English
    Publishing date 2023-03-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2756371-6
    ISSN 2326-5205 ; 2326-5191
    ISSN (online) 2326-5205
    ISSN 2326-5191
    DOI 10.1002/art.42382
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: P2Y12 Inhibition Suppresses Proinflammatory Platelet-Monocyte Interactions.

    Rolling, Christina C / Sowa, Marcin A / Wang, Tricia T / Cornwell, MacIntosh / Myndzar, Khrystyna / Schwartz, Tamar / El Bannoudi, Hanane / Buyon, Jill / Barrett, Tessa J / Berger, Jeffrey S

    Thrombosis and haemostasis

    2023  Volume 123, Issue 2, Page(s) 231–244

    Abstract: Background:  Monocyte-platelet aggregates (MPAs) represent the crossroads between thrombosis and inflammation, and targeting this axis may suppress thromboinflammation. While antiplatelet therapy (APT) reduces platelet-platelet aggregation and ... ...

    Abstract Background:  Monocyte-platelet aggregates (MPAs) represent the crossroads between thrombosis and inflammation, and targeting this axis may suppress thromboinflammation. While antiplatelet therapy (APT) reduces platelet-platelet aggregation and thrombosis, its effects on MPA and platelet effector properties on monocytes are uncertain.
    Objectives:  To analyze the effect of platelets on monocyte activation and APT on MPA and platelet-induced monocyte activation.
    Methods:  Agonist-stimulated whole blood was incubated in the presence of P-selectin, PSGL1, PAR1, P2Y
    Results:  Consistent with a proinflammatory platelet effector role, MPAs were increased in patients with COVID-19. RNA-Seq revealed a thromboinflammatory monocyte transcriptome upon incubation with platelets. Monocytes aggregated to platelets expressed higher CD40 and tissue factor than monocytes without platelets (
    MeSH term(s) Humans ; Blood Platelets/metabolism ; COVID-19 ; Inflammation/metabolism ; Monocytes/metabolism ; P-Selectin/metabolism ; Platelet Activation ; Platelet Glycoprotein GPIIb-IIIa Complex/metabolism ; Platelet Membrane Glycoprotein IIb/metabolism ; Receptor, PAR-1/metabolism ; Thrombosis/metabolism
    Chemical Substances P-Selectin ; Platelet Glycoprotein GPIIb-IIIa Complex ; Platelet Membrane Glycoprotein IIb ; Receptor, PAR-1 ; P2RY12 protein, human
    Language English
    Publishing date 2023-01-11
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 518294-3
    ISSN 2567-689X ; 0340-6245
    ISSN (online) 2567-689X
    ISSN 0340-6245
    DOI 10.1055/s-0042-1758655
    Database MEDical Literature Analysis and Retrieval System OnLINE

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