Aspirin enhances regulatory functional activities of monocytes and downregulates CD16 and CD40 expression in myocardial infarction autoinflammatory disease

Belhassena, Imène; Nouari, Wafa; Messaoud, Aida; Nouar, Mouna; Brahimi, Mohamed; Lamara, Sid-Ahmed Chawki; Aribi, Mourad

doi:10.1016/j.intimp.2020.106349

Cited by 8 publications

(5 citation statements)

References 114 publications

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“…In a different way of our data, the results presented by Belhassena et al (2020) in a study in which the authors evaluated the effects of aspirin (acetylsalicylic acid-ASA) on immunomodulation of monocytes from patients with AMI and controls, the cells treated ex vivo with different concentrations of ASA showed a phenotypic modulation of the monocytes to a lower expression of CD16, and considered these cells as an anti-inflammatory profile. These apparently contradictory findings might be related to the different methodological aspects: 1) antiplatelet drugs utilized (in our study we used clopidogrel and ticagrelor); 2) the monocytes were treated ex vivo for few hours in the Belhassena study; and, 3) few patients were analyzed by Belhassena. In the current study, we suggest a persistence of the inflammatory phenotype after 6 months of treatment, despite the highly-effective lipid-lowering and antiplatelet therapies, due to an increase in classical (proinflammatory) monocytes and a reduction in non-classical (antiinflammatory) monocytes.…”

Section: Discussionmentioning

confidence: 85%

Monocytes presenting a pro-inflammatory profile persist in patients submitted to a long-term pharmacological treatment after acute myocardial infarction

Carvalho

Fonseca²,

Izar³

et al. 2023

Front. Physiol.

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Introduction: Although it is broadly known that monocyte recruitment is involved in atherosclerosis development and that, in accordance with the microenvironment, these cells can be modulated into three well-known subpopulations: Classical (CD14++CD16−), intermediate (CD14++CD16+), and non-classical (CD14+CD16++), the effects of treatment with different pharmacological strategies (based on lipid-lowering and antiplatelets) after acute myocardial infarction upon the monocytes modulation and the role of the chemokine receptors CCR2, CCR5 and CX3CR1 in this context, are poorly understood.Methods: In this study, patients [n = 148, both men (n = 105, 71%) and women (n = 43, 29%)] submitted to treatment with a 2×2 factorial design, in which they received rosuvastatin 20 mg or simvastatin 40 mg plus ezetimibe 10 mg, as well as ticagrelor 90 mg or clopidogrel 75 mg were enrolled. Monocyte subsets were analyzed by flow cytometry at baseline (BL), and after one (1-M) and 6 months (6-M) of treatment.Results: Firstly, our results showed that, regardless of the treatment received, higher percentages of classical monocytes and lower of non-classical monocytes were found at the 6-M time point than BL values, whilst the percentage of intermediate monocytes was higher in all time points assessed than the other subsets. There were reductions in the CCR2 expression by non-classical and intermediate monocytes, without differences for the classical subtype. Concerning the CCR5 expression, there were reductions in the three monocyte subtypes, whereas the CX3CR1 expression increased both in intermediate and classical monocytes, without differences for non-classical monocytes. In relation to the treatment received, a higher percentage of intermediate monocytes at the 6-M time point than the values BL was observed in the group treated with simvastatin + ezetimibe + clopidogrel. No significant differences were found concerning non-classical, intermediate, and classical monocytes, for CCR2, CCR5, and CX3CR1 in the four treatment arms.Conclusion: Taken together, our results demonstrated that even under lipid-lowering and antiplatelet therapy for 6 months, the inflammatory phenotype of monocytes still persisted in the patients enrolled in this study.

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Section: Discussionmentioning

confidence: 85%

Monocytes presenting a pro-inflammatory profile persist in patients submitted to a long-term pharmacological treatment after acute myocardial infarction

Carvalho

Fonseca²,

Izar³

et al. 2023

Front. Physiol.

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“…This demonstrates the efficiency of CD40R in predicting the presence of a high atherosclerotic burden among real-word, high risk subjects in whom this estimation cannot be done with sufficient accuracy using traditional approaches. The slightly higher prevalence rate of statin and antiplatelet drug use in the higher tertile of CD40R might have produced, if any, an underestimation of the discriminating power of CD40R, since in vitro both drugs have been proved to inhibit CD40R expression in human vascular cells (48,49) . We tested this hypothesis through a multilevel interaction model analysis between statins, antiplatelet and CD40R considering the total plaque area as outcome and adjusted from potential confounders.…”

Section: Discussionmentioning

confidence: 99%

Soluble CD40 receptor is a biomarker of the burden of carotid artery atherosclerosis in subjects at high cardiovascular risk

et al. 2022

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“…[40] To further probe the immunomodulatory effects of dendrimer 1 in comparison to GA, we measured levels of CD14, CD16, CD68, CCR2 and HLA-DR as typical markers of monocyte inflammatory activation, and of CD206 as marker of the M2 anti-inflammatory phenotype (Figure 4 ae, Figure S6-11). [41][42][43][44][45][46][47] Under non-activated conditions, dendrimer 1 downregulated the innate immune response receptors CD14 (LPS receptor), CD16 (Fcg receptor III), HLA-DR (Human leukocyte antigen class II) [48] and CD68 (peptide transport, antigen processing), indicative of a general immunosuppressive property (Figure 4 b). Dendrimer 1 also downregulated the chemokine receptor CCR2, which is often used as a marker for M1 (pro-inflammatory state) [49,50] and upregulated CD206, (Figure 4 a-c), a mannose receptor used as marker for M2 (anti-inflammatory state).…”

Section: Methodsmentioning

confidence: 99%

An Immunomodulatory Peptide Dendrimer Inspired from Glatiramer Acetate

et al. 2021

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Glatiramer acetate (GA) is a random polypeptide drug used to treat multiple sclerosis (MS), a chronic autoimmune disease. With the aim of identifying a precisely defined alternative to GA, we synthesized a library of peptide dendrimers with an amino acid composition similar to GA. We then challenged the dendrimers to trigger the release of the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1Ra) from human monocytes, which is one of the effects of GA on immune cells. Several of the largest dendrimers tested were as active as GA. Detailed profiling of the best hit showed that this dendrimer induces the differentiation of monocytes towards an M2 (anti-inflammatory) state as GA does, however with a distinct immune marker profile. Our peptide dendrimer might serve as starting point to develop a well-defined immunomodulatory analog of GA.

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Aspirin enhances regulatory functional activities of monocytes and downregulates CD16 and CD40 expression in myocardial infarction autoinflammatory disease

Cited by 8 publications

References 114 publications

Monocytes presenting a pro-inflammatory profile persist in patients submitted to a long-term pharmacological treatment after acute myocardial infarction

Monocytes presenting a pro-inflammatory profile persist in patients submitted to a long-term pharmacological treatment after acute myocardial infarction

Soluble CD40 receptor is a biomarker of the burden of carotid artery atherosclerosis in subjects at high cardiovascular risk

An Immunomodulatory Peptide Dendrimer Inspired from Glatiramer Acetate

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