Circulating monocyte-platelet aggregates are a robust marker of platelet activity in cardiovascular disease

Allen, Nicole; Barrett, Tessa J.; Guo, Yu; Nardi, Michael A.; Ramkhelawon, Bhama; Rockman, Caron; Hochman, Judith S.

doi:10.1016/j.atherosclerosis.2018.12.029

Cited by 89 publications

(82 citation statements)

References 43 publications

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“…The NLRP3 inflammasome is primarily assembled in myeloid cells. Although activated platelets are known to form aggregates with immune cells and modulate their function (Allen et al, 2019; Dann et al, 2018; Kral et al, 2016; Passacquale et al, 2011b) the effect of platelets on inflammasome activation in innate immune cells remains unexplored. To address this question, we investigated the influence of platelets on the production of IL-1 cytokines elicited by the bona fide NLRP3 inflammasome activators Nigericin and ATP in mouse and human immune cells.…”

Section: Resultsmentioning

confidence: 99%

“…In the last decade, platelets have been increasingly recognized of their roles in immunity (Allen et al, 2019; Dann et al, 2018; Kral et al, 2016; Passacquale et al, 2011a). Approximately one trillion platelets (150– 450 × 10 9 /L) circulate in the blood of a healthy individual, a number that surpasses all other leukocytes in the vasculature by several folds.…”

Section: Introductionmentioning

confidence: 99%

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Platelets fuel the inflammasome activation of innate immune cells

Rolfes

Ribeiro

Hawwari

et al. 2019

Preprint

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ABSTRACTThe inflammasomes control the bioactivity of pro-inflammatory cytokines of the interleukin (IL)-1 family. The inflammasome assembled by NLRP3 has been predominantly studied in homogenous cell populations in vitro, neglecting the influence of cellular interactions that occur in vivo. Here, we show that platelets, the second most abundant cells in the blood, boost the inflammasome capacity of human macrophages and neutrophils, and are critical for IL-1 production by monocytes. Platelets license NLRP3 transcription, thereby enhancing ASC nucleation, caspase-1 activity, and IL-1β maturation. Platelet depletion attenuated LPS-induced IL-1β in vivo, and platelet counts correlate with plasma concentrations of IL-1β in malaria patients. Furthermore, a platelet gene signature was enriched among the highest expressed transcripts in IL-1β-driven autoinflammatory diseases. The platelet-mediated enhancement of inflammasome activation was independent of cell-to-cell contacts, platelet-derived lipid mediators, purines, nucleic acids and a host of platelet cytokines, and involved the triggering of calcium sensing receptors on macrophages by a calcium-dependent protein commonly released by platelets and megakaryocytes. Finally, we report that platelets provide an additional layer of regulation of inflammasomes in vivo.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Platelets fuel the inflammasome activation of innate immune cells

Rolfes

Ribeiro

Hawwari

et al. 2019

Preprint

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“…Circulating MPA could be a sensitive marker of platelet activity and monocyte inflammation. 7,21 Immunoreaction between Pselectin and circulating monocytes to form MPAs has been recognized as one of the atherothrombosis mechanisms. 22,23 MPA levels were previously found to be higher in ACS patients.…”

Section: P-selectin On the Platelet Surface: The Interaction With Rocmentioning

confidence: 99%

“…This cascade promotes plaque rupture and results in atherothrombosis. 4 An increasing number of clinical studies [5][6][7] show that platelets form monocyte-platelet aggregates (MPAs) in circulation. Elevated circulating MPAs have been found to be associated with atherothrombosis and indicate a high risk for plaque rupture and thrombus burden in vascular occlusive diseases.…”

Section: Introductionmentioning

confidence: 99%

The Role of ROCK in Platelet–Monocyte Collaborative Induction of Thromboinflammation during Acute Coronary Syndrome

et al. 2020

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Background Arterial thrombosis is initiated by atherosclerotic plaque damage, prothrombotic material release and platelet aggregation. Platelets are primary mediators involved in thrombosis and cooperate with vascular and immune cells. Objective Herein, we investigated how activated platelets interacted with monocytes in atherothrombosis. Methods and Results We collected patients' blood from coronary arteries during percutaneous coronary intervention and measured platelet activity. Platelets from coronary arteries had higher pseudopodium expression and activity in patients with acute coronary syndrome (ACS). Ribosome profiling of platelets from coronary blood mapped a vigorous upregulation of Rho GTPases and their downstream effectors. RhoA activated downstream Rho-associated coiled-coil containing protein kinase (ROCK), and ROCK increased surface P-selectin in coronary blood platelets. The interaction between platelets and monocytes was observed in vitro, and was found in ruptured coronary plaques of ACS. Further we found that activated platelets promoted monocytes transmigration, which could be suppressed in the presence of ROCK inhibitors. The increased surface P-selectin on thrombin-induced platelets interacted with monocytes to upregulate monocyte chemokine receptor 2 (CCR2) expression via the ROCK pathway. The expression of CCR2 was higher in monocyte–platelet aggregates than in monocytes without platelets. Finally, using the Asian Screening Array BeadChip, we identified single-nucleotide polymorphism (SNP) associated with cardiovascular events. Notably, patients having homozygous major alleles of the RHOA SNP rs11706370 presented with higher risks of cardiovascular events. Conclusion Through ROCK-activated cytoskeleton remodeling and P-selectin expression, platelets were recruited and interacted synergistically with high CCR2-expressing monocytes to induce thromboinflammation in atherothrombosis.

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“…However, there were some limitations in this study. First, although previous study demonstrated the predictive value of platelet counts for thrombosis and cardiovascular diseases [30] , using platelet counts alone to represent coagulation might limit the speci city blood coagulation assessment and future study should include more speci c biomarkers. However, low test cost and easy availability make platelet counts more suitable for large-scale epidemiological studies compared to other biomarkers.…”

mentioning

confidence: 99%

Effects of long-term particulate matter exposure on platelet counts in adults of Northeast China

Zhang¹,

Zhao²

2020

Preprint

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Associations between air pollution exposure and platelet counts have been inconsistent in previous studies, and there have been few studies of effects of long-term exposure in Asian populations. We explored the associations between long-term PM2.5 (particulate matter < 2.5 µm) exposure and platelet counts using a prospective cohort study in Northeast China. We used a logistic regression model to analyze the effects of different PM2.5 increments and platelet count elevation. Mixed linear models were used to analyze the association between PM2.5 concentration and platelet counts. Interaction and stratified analyses were also conducted. Results showed that every 1 µg/m3 increment of PM2.5 exposure was associated with 0.29% (95%CI: 0.25–0.32%) increase in platelet counts and 10% (95%CI: 8–12%) higher risk of platelet elevation. Effects of long-term PM2.5 exposure on platelet elevation were stronger in male participants, of Han ethnicity, and without diabetes. Our findings add more evidence to the potential biological mechanisms responsible for the effect of air pollution exposure on cardiovascular disease.

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Circulating monocyte-platelet aggregates are a robust marker of platelet activity in cardiovascular disease

Cited by 89 publications

References 43 publications

Platelets fuel the inflammasome activation of innate immune cells

Platelets fuel the inflammasome activation of innate immune cells

The Role of ROCK in Platelet–Monocyte Collaborative Induction of Thromboinflammation during Acute Coronary Syndrome

Effects of long-term particulate matter exposure on platelet counts in adults of Northeast China

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