Monocyte-platelet aggregates affect local inflammation in patients with acute myocardial infarction

Kossmann, Hans; Rischpler, Christoph; Hanus, Franziska; Nekolla, Stephan G.; Kunze, Karl; Götze, Katharina; Goedel, Alexander; Sager, Hendrik B.; Kastrati, Adnan; Sinnecker, Daniel; Kupatt, Christian; Ibrahim, Tareq; Schwaiger, Markus; Laugwitz, Karl‐Ludwig; Dirschinger, Ralf J.

doi:10.1016/j.ijcard.2019.04.009

Cited by 17 publications

(10 citation statements)

References 47 publications

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“…Peak uptake of 18 F-FDG within the ischaemic heart occurs approximately 3-5 days post-MI and declines over 7-14 days; this is in line with the time course of accumulation of proinflammatory M1-like macrophages and CD11b-positive monocytes [79][80][81]. 18 F-FDG PET combined with magnetic resonance imaging (MRI) has confirmed the biphasic nature of inflammatory and reparative monocyte infiltration into the infarcted heart in a murine model as well as in patients with acute MI [79,82]. Intriguingly, Rischpler and colleagues showed that 18 F-FDG uptake 5 days after percutaneous coronary intervention (PCI) in patients with MI had an inverse correlation with the cardiac functional outcome measured by MRI 6-9 months post-MI, demonstrating that 18 F-FDG imaging can serve as a prognostic biomarker for MI [1].…”

Section: Glucose Metabolismsupporting

confidence: 55%

Imaging Inflammation with Positron Emission Tomography

et al. 2021

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The impact of inflammation on the outcome of many medical conditions such as cardiovascular diseases, neurological disorders, infections, cancer, and autoimmune diseases has been widely acknowledged. However, in contrast to neurological, oncologic, and cardiovascular disorders, imaging plays a minor role in research and management of inflammation. Imaging can provide insights into individual and temporospatial biology and grade of inflammation which can be of diagnostic, therapeutic, and prognostic value. There is therefore an urgent need to evaluate and understand current approaches and potential applications for imaging of inflammation. This review discusses radiotracers for positron emission tomography (PET) that have been used to image inflammation in cardiovascular diseases and other inflammatory conditions with a special emphasis on radiotracers that have already been successfully applied in clinical settings.

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Section: Glucose Metabolismsupporting

confidence: 55%

Imaging Inflammation with Positron Emission Tomography

et al. 2021

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“…Importantly, the increase of MPA in other patient populations such as those with CVDs, including chronic atherosclerosis and myocardial infarction (MI), 2 10 37 38 39 is indicative of similarities in the pathophysiology of inflammatory diseases with enhanced risk of prothrombotic complications.…”

Section: Discussionmentioning

confidence: 99%

P2Y12 Inhibition Suppresses Proinflammatory Platelet–Monocyte Interactions

et al. 2023

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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, P2Y12, GP IIb/IIIa, and COX-1 inhibitors and assessed for platelet and monocyte activity via flow cytometry. RNA-Seq of monocytes incubated with platelets was used to identify platelet-induced monocyte transcripts and was validated by RT-qPCR in monocyte-PR co-incubation ± APT. 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 (p < 0.05 for each). Inhibition with P-selectin (85% reduction) and PSGL1 (87% reduction) led to a robust decrease in MPA. P2Y12 and PAR1 inhibition lowered MPA formation (30 and 21% reduction, p < 0.05, respectively) and decreased monocyte CD40 and TF expression, while GP IIb/IIIa and COX1 inhibition had no effect. Pretreatment of platelets with P2Y12 inhibitors reduced the expression of platelet-mediated monocyte transcription of proinflammatory SOCS3 and OSM. Conclusions Platelets skew monocytes toward a proinflammatory phenotype. Among traditional APTs, P2Y12 inhibition attenuates platelet-induced monocyte activation.

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“…[11][12][13] In addition, MPAs affect local inflammation and development of left ventricular dysfunction after myocardial infarction. 12,26 As a marker of platelet activation, MPA may be influenced by antiplatelet therapy. However, as previously shown, MPA formation was not significantly affected by aspirin treatment, 15 and MPA levels did not differ significantly between patients without and with poor response to clopidogrel, 16 suggesting no pronounced effects of these antiplatelet drugs on MPA formation.…”

Section: Discussionmentioning

confidence: 99%

Circulating MicroRNAs and Monocyte–Platelet Aggregate Formation in Acute Coronary Syndrome

et al. 2021

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Background Monocyte–platelet aggregates (MPAs) are a sensitive marker of in vivo platelet activation in acute coronary syndrome (ACS) and associated with clinical outcomes. MicroRNAs (miRs) play an important role in the regulation of platelet activation, and may influence MPA formation. Both, miRs and MPA, could be influenced by the type of P2Y12 inhibitor. Aim To study the association of platelet-related miRs with MPA formation in ACS patients on dual antiplatelet therapy (DAPT), and to compare miRs and MPA levels between prasugrel- and ticagrelor-treated patients. Methods and Results We analyzed 10 circulating platelet-related miRs in 160 consecutive ACS patients on DAPT with low-dose aspirin and either prasugrel (n = 80) or ticagrelor (n = 80). MPA formation was measured by flow cytometry without addition of platelet agonists and after simulation with the toll-like receptor (TLR)-1/2 agonist Pam3CSK4, adenosine diphosphate (ADP), or arachidonic acid (AA). In multivariate regression analyses, we identified miR-21 (β = 9.50, 95% confidence interval [CI]: 1.60–17.40, p = 0.019) and miR-126 (β = 7.50, 95% CI: 0.55–14.44, p = 0.035) as independent predictors of increased MPA formation in vivo and after TLR-1/2 stimulation. In contrast, none of the investigated miRs was independently associated with MPA formation after stimulation with ADP or AA. Platelet-related miR expression and MPA formation did not differ significantly between prasugrel- and ticagrelor-treated patients. Conclusion Platelet-related miR-21 and miR-126 are associated with MPA formation in ACS patients on DAPT. miRs and MPA levels were similar in prasugrel- and ticagrelor-treated patients.

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Monocyte-platelet aggregates affect local inflammation in patients with acute myocardial infarction

Cited by 17 publications

References 47 publications

Imaging Inflammation with Positron Emission Tomography

Imaging Inflammation with Positron Emission Tomography

P2Y12 Inhibition Suppresses Proinflammatory Platelet–Monocyte Interactions

Circulating MicroRNAs and Monocyte–Platelet Aggregate Formation in Acute Coronary Syndrome

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