Platelet-monocyte Aggregation Research Articles

Recent Advances on the Molecular Mechanism and Clinical Trials of Venous Thromboembolism.

Venous thromboembolism is a condition that includes deep vein thrombosis and pulmonary embolism. It is the third most common cardiovascular disease behind acute coronary heart disease and stroke. Over the past few years, growing research suggests that venous thrombosis is also related to the immune system and inflammatory factors have been confirmed to be involved in venous thrombosis. The role of inflammation and inflammation-related biomarkers in cerebrovascular thrombotic disease is the subject of ongoing debate. P-selectin leads to platelet-monocyte aggregation and stimulates vascular inflammation and thrombosis. The dysregulation of miRNAs has also been reported in venous thrombosis, suggesting the involvement of miRNAs in the progression of venous thrombosis. Plasminogen activator inhibitor-1 (PAI-1) is a crucial component of the plasminogen-plasmin system, and elevated levels of PAI-1 in conjunction with advanced age are significant risk factors for thrombosis. In addition, it has been showed that one of the ways that neutrophils promote venous thrombosis is the formation of neutrophil extracellular traps (NETs). In recent years, the role of extracellular vesicles (EVs) in the occurrence and development of VTE has been continuously revealed. With the advancement of research technology, the complex regulatory role of EVs on the coagulation process has been gradually discovered. However, our understanding of the causes and consequences of these changes in venous thrombosis is still limited. Therefore, we review our current understanding the molecular mechanisms of venous thrombosis and the related clinical trials, which is crucial for the future treatment of venous thrombosis.

Subclinical cardiovascular outcomes of acute exposure to fine particulate matter and its constituents: A glutathione S-transferase polymorphism-based longitudinal study

To explore the acute subclinical cardiovascular effects of fine particulate matter (PM2.5) and its constituents, a longitudinal study with 61 healthy young volunteers was conducted in Xinxiang, China. Linear mixed-effect models were used to analyze the association of PM2.5 and its constituents with cardiovascular outcomes, respectively, including blood pressure (BP), heart rate (HR), serum levels of high-sensitivity C-reactive protein (hs-CRP), 8-hydroxy-2′-deoxyguanosine (8-OHdG), tissue-type plasminogen activator (t-PA), and platelet-monocyte aggregation (PMA). Additionally, the modifying effects of glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) polymorphisms were examined. A 10 μg/m3 increase in PM2.5 was associated with −1.04 (95 % CI: −1.86 to −0.22) mmHg and −0.90 (95 % CI: −1.69 to −0.11) mmHg decreases in diastolic BP (DBP) and mean arterial BP (MABP) along with 1.83 % (95 % CI: 0.59–3.08 %), 5.93 % (95 % CI: 0.70–11.16 %) increases in 8-OHdG and hs-CRP, respectively. Ni content was positively associated with the 8-OHdG levels whereas several other metals presented negative association with 8-OHdG and HR. Intriguingly, GSTT1+/GSTTM1+ subjects showed higher susceptibility to PM2.5-induced alterations of DBP and PMA, and GSTT1-/GSTM1+ subjects showed higher alteration on t-PA. Taken together, our findings indicated that short-term PM2.5 exposure induced oxidative stress, systemic inflammation, autonomic alterations, and fibrinolysis in healthy young subjects. Among multiple examined metal components Ni appeared to positively associated with systematic oxidative stress. In addition, GST-sufficient subjects might be more prone to PM2.5-induced autonomic alterations.

A PSGL-1 glycomimetic reduces thrombus burden without affecting hemostasis

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What's New in Shock, February 2021?

What's New in Shock, February 2021?

Short time exposure to ambient ozone and associated cardiovascular effects: A panel study of healthy young adults

The evidence that exposure to ambient ozone (O3) causes acute cardiovascular effects appears inconsistent. A repeated-measure study with 61 healthy young volunteers was conducted in Xinxiang, Central China. Real-time concentrations of O3 were monitored. Cardiovascular outcomes including blood pressure (BP), heart rate (HR), serum levels of high sensitivity C-reactive protein (hs-CRP), 8-hydroxy-2′-deoxyguanosine (8-OHdG), tissue-type plasminogen activator (t-PA), and platelet-monocyte aggregation (PMA) were repeated measured. Linear mixed-effect models were used to analyze the association of ambient O3 with these cardiovascular outcomes. Additionally, the modifying effects of glutathione S-transferase mu 1 (GSTM1) and glutathione S-transferase theta 1 (GSTT1) polymorphisms were estimated to explore the potential mechanisms and role of the association between O3 exposure and the above cardiovascular outcomes. A 10 μg/m3 increase in O3 was associated with increases of 9.2 mmHg (95% confidence interval [CI]: 2.5, 15.9), 7.2 mmHg (95% CI: 0.8, 13.6), and 21.2 bpm (95% CI: 5.8, 36.6) in diastolic BP (DBP, lag1), mean arterial BP (MABP, lag1), and HR (lag01), respectively. Meanwhile, the serum concentrations of hs-CRP, 8-OHdG, and t-PA were all increased by O3 exposure, but the PMA level was decreased. Stratification analyses showed that the estimated effects of O3 on DBP, MABP, and HR in GSTM1-sufficient subjects were significantly higher than in GSTM1-null subjects. Moreover, GSTM1-null genotype enhanced O3-induced increases, albeit insignificant, in levels of serum hs-CRP, 8-OHdG, and t-PA compared with GSTM1-sufficient genotype. Insignificant increases in hs-CRP and t-PA were also detected in GSTT1-null subjects. Taken together, our findings indicate that acute exposure to ambient O3 induces autonomic alterations, systemic inflammation, oxidative stress, and fibrinolysis in healthy young subjects. GSTM1 genotype presents the trend of modifying O3-induced cardiovascular effects.

Impaired Glucose Tolerance is Associated with Enhanced Platelet-Monocyte Aggregation in Short-Term High-Fat Diet-Fed Mice.

High-fat diet (HFD) feeding is known to induce metabolic dysregulation, however, less is known on its impact in promoting the hypercoagulable state. This current study aimed to evaluate platelet-monocyte aggregate (PMA) formation following short-term HFD feeding. This is particularly important for understanding the link between inflammation and the hypercoagulable state during the early onset of metabolic dysregulation. To explore such a hypothesis, mice were fed a HFD for 8 weeks, with body weights as well as insulin and blood glucose levels monitored on a weekly basis during this period. Basal hematological measurements were determined and the levels of spontaneous peripheral blood PMAs were assessed using whole blood flow cytometry. The results showed that although there were no significant differences in body weights, mice on HFD displayed impaired glucose tolerance and markedly raised insulin levels. These metabolic abnormalities were accompanied by elevated baseline PMA levels as an indication of hypercoagulation. Importantly, it was evident that baseline levels of monocytes, measured using the CD14 monocyte marker, were significantly decreased in HFD-fed mice when compared to controls. In summary, the current evidence shows that in addition to causing glucose intolerance, such as that identified in a prediabetic state, HFD-feeding can promote undesirable hypercoagulation, the major consequence implicated in the development of cardiovascular complications.

Coenzyme Q10 Attenuates Platelet Integrin αIIbβ3 Outside-in Signaling through Targeting cAMP/PKA Pathway and Inhibits Atherosclerosis

Introduction: Platelet integrin αIIbβ3 outside-in signaling is crucial for platelet adhesion and aggregation, and contributes to atherogenesis. Coenzyme Q10 (CoQ10) has been implicated as a protective factor against cardiovascular diseases (CVDs), particularly atherosclerosis. However, whether CoQ10 attenuates atherosclerosis through inhibiting platelet function and αIIbβ3 outside-in signaling is unknown. The aim of this study was to explore whether CoQ10 affects platelet function and αIIbβ3 outside-in signalling and thus inhibiting the progress of atherosclerosis in vivo and the underlying mechanisms in vitro.Methods:In vitro study, The murine platelet rich plasma (PRP) from C57BL/6J wild-type (WT) mice or human PRP and gel-filtered platelets were incubated with different concentrations (1, 10 or 100 μM) of CoQ10 or the vehicle control for 50 min. Platelet aggregation, spreading on fibrinogen (Fg) and clot retraction were determined. In addition, the effects of CoQ10 on platelet integrin αIIbβ3 inside-out signalling (e.g., talin-1 and kindlin-3 binding to integrin β3) were determined by immunoprecipitation, and outside-in signalling (e.g., phosphorylation of sarcoma tyrosine-protein kinase (c-Src), focal adhesion kinase (FAK), and β3 cytoplasmic tail, myosin light chain (MLC)) were determined by Western blotting. The levels of platelet ATP and cAMP were measured by ELISA assays. In vivo study, male homozygous apolipoprotein E-deficient (apoE-/-) mice (C57BL/6 genetic background) were fed either a standard normal AIN-93G diet (NC group), a Western-type diet (HFD group) or a Western-type diet supplemented with CoQ10 (1800 mg/kg diet) (CoQ10 group) for 12 weeks. Platelet aggregation, granule secretion, platelet spreading, clot retraction, integrin αIIbβ3 outside-in signalling, platelet-leukocyte interactions and carotid artery plaque area were also examined. In our randomized, double-blind, placebo-controlled trial, 101 hypercholesterolemic subjects were randomly administrated to 120 mg CoQ10 or placebo daily for 24 weeks. Platelet intracellular CoQ10 levels, platelet aggregation in PRP, platelet platelet factor 4 (PF-4) and C-C motif ligand 5 (CCL5) release, and platelet integrin αIIbβ3 outside-in signalling were also evaluated before and after 24 weeks of intervention.Results: We found that CoQ10 inhibited human and WT mouse platelet aggregation, platelet spreading, granule secretion, and clot retraction in vitro and apoE-/- mice on a high fat diet. CoQ10 also reduced atherosclerosis and platelet-monocyte aggregation in apoE-/- mice. The inhibitory effects of CoQ10 is mediated by attenuated αIIbβ3 outside-in signalling pathway (e.g., attenuation of phosphorylation of c-Src, FAK, and β3 cytoplasmic tail, and MLC in thrombin-activated platelets or platelets exposed to immobilized Fg), which requires up-regulation of the cAMP/PKA pathway, where CoQ10 inhibited phosphodiesterase 3A activity and activated the A2A adenosine receptor. However, CoQ10 did not affect platelet integrin αIIbβ3 inside-out signalling pathway, platelet cellular ATP, or platelet apoptosis (the mitochondrial membrane potential and phosphatidylserine exposure). Moreover, our clinical trial in dyslipidemic patients demonstrated that CoQ10 supplementation attenuated platelet aggregation, which was positively correlated with the increased platelet CoQ10 concentrations, inhibited αIIbβ3 outside-in signalling and decreased platelet PF-4 and CCL5 secretion.Conclusions: We present new data to suggest that CoQ10 plays a novel role in attenuating platelet function and integrin αIIbβ3 outside-in signalling though targeting cAMP/PKA signalling cascade and thus inhibiting the progress of atherosclerosis. CoQ10 is therefore a promising agent for the prevention and/or treatment for cardiovascular disease. DisclosuresNo relevant conflicts of interest to declare.

A switch to a raltegravir containing regimen does not lower platelet reactivity in HIV-infected individuals.

Platelet hyperreactivity and increased platelet-monocyte aggregation (PMA) are associated with increased cardiovascular risk and inflammation. In a previous cross-sectional study, individuals using a raltegravir (RAL)-based regimen were found to have reduced platelet reactivity and PMA compared with other antiretroviral regimens. Our aim was to investigate whether switching from a nonintegrase inhibitor regimen to a RAL-based regimen reduces platelet reactivity or PMA. An investigator initiated, single-centre, prospective randomized, open-label, blinded endpoint trial. Forty HIV-infected adults using a nonintegrase inhibitor containing regimen with undetectable viral load were randomized to either continue their regimen or switch to a RAL-based regimen for 10 weeks, continuing the same backbone. The primary outcome was the change in platelet reactivity at week 10, which was determined as the expression of the platelet activation marker P-selectin and binding of fibrinogen before and after ex-vivo stimulation with different platelet agonists. Secondary outcomes included PMA, plasma markers of platelet activation and markers of inflammation and immune cell activation. Twenty-one participants were enrolled in the continuation group and 19 in the RAL group. Baseline characteristics were comparable between groups. There were no differences in the change in platelet reactivity to either platelet agonist at week 10, nor in plasma markers of platelet activation. PMA, C-reactive protein, T-cell activation (CD38HLA-DR) and monocyte (CD14CD16) subsets. Switching a nonintegrase inhibitor containing regimen to a RAL-based regimen does not reduce platelet reactivity, platelet-leukocyte aggregation, inflammation and immune activation in virologically suppressed HIV-infected individuals. NCT02383355.

Platelet reactivity in diabetic patients with invasive Klebsiella pneumoniae liver abscess syndrome.

ObjectivePlatelets catalyze the development of hyperinflammation and microthrombosis and contribute to increases in accumulation of circulating platelet-leukocyte complex, the key event in the development of disseminated infection.Subjects and methodsTo determine the relationships of platelet activity in diabetic patients with invasive Klebsiella pneumoniae liver abscess syndrome (IKLAS), a total of 175 diabetic patients with community-acquired Klebsiella pneumoniae (KP) bacteremia were included in this study. We compared the platelet reactivity of 40 patients with IKLAS, 40 patients with non-IKLAS, and eight healthy controls using a whole-blood flow cytometry-based assay.ResultsPatients who were infected with strains expressing K1/K2 serotype (adjusted odds ratio [AOR], 8.81; 95% CI, 2.18–35.53) and those with HbA1c ≥9% (AOR, 4.97; 95% CI, 1.73–14.23) were more likely to present with IKLAS, whereas those who had recent therapy with aspirin (AOR, 0.17; 95% CI, 0.04–0.79) were less likely to present with IKLAS. Among patients with IKLAS, patients with a poor glycemic control were more likely to present with hepatic venous thrombo-phlebitis than those with suboptimal or good glycemic control (P=0.03). Patients with IKLAS had a higher median fluorescence intensity of the platelet membrane expression of P-selectin than those with non-IKLAS (78.0 vs 28.0, P<0.001) and controls (78.0 vs 22.0, P< 0.001). The IKLAS group also demonstrated a significantly higher platelet-monocyte aggregation and higher plasma levels of PF-4 than the non-IKLAS group (47.0 vs 18.0 and 47.0 vs 4.0, respectively, both P <0.001) and controls (46.0 vs 24.0 and 46.0 vs 13.0, respectively, both P <0.001).ConclusionDiabetic patients with IKLAS demonstrated platelet hyperreactivity, which may be associated with a higher risk for vascular complications.

Prothrombotic mechanisms in patients with congenital p.Cys89Tyr mutation in CD59

BackgroundThrombosis is the prognostic factor with the greatest effect on survival in patients with paroxysmal nocturnal hemoglobinuria (PNH), who lack dozens of membrane surface proteins. We recently described a primary homozygous Cys89Tyr congenital nonfunctioning CD59 in humans with clinical manifestation in infancy, associated with chronic hemolysis, recurrent strokes, and relapsing peripheral demyelinating neuropathy. Here we investigated hypercoagulability mechanisms characterizing the syndrome. MethodsMembrane attack complex (MAC) deposition (anti-SC5b-9) and free hemoglobin (colorimetric assay) were assessed. Platelet activation was identified (anti-CD61, anti-CD62P), and microparticles (MPs) of 0.5–0.9 μm, were characterized (Annexin V, anti-human GlyA, anti-CD15, anti-CD14, anti-CD61). Platelet-monocyte aggregation was assessed with FlowSight. Findings2/7 patients (29%) with homozygosity for Cys89Tyr and 6/12 (50%) with any of four described CD59 mutations had recurrent strokes. In plasma samples from four patients carrying identical mutations, MAC deposition was increased on RBCs (p < 0.0003), neutrophils (p < 0.009), and platelets (p < 0.0003). Free-plasma hemoglobin levels were abnormally high, up to 100 mg/dl. Patients with CD59 mutation had RBC-derived MP levels 9-fold higher than those in healthy controls (p < 0.01), and 2–2.5 fold higher than PNH patients (p < 0.09). Leukocyte-activated platelet aggregation was increased (p < 0.0062). Loss of CD59 was shown in the endothelium of these patients. InterpretationNonfunctioning CD59 is a major risk factor for stroke and hypercoagulability. Uncontrolled hemolysis causes massive MP release and endothelial heme damage. MAC attack on unprotected endothelium and platelet activation and aggregation with leukocytes mediate additional mechanisms leading to vascular occlusion. It is suggested that CD59 loss represents a major arterial prothrombotic factor in PNH and additional diseases.

Platelet-monocyte interaction in Mycobacterium tuberculosis infection

The immune effects of platelets and platelet-leukocyte aggregation are increasingly recognized. We studied the occurrence of platelet-monocyte aggregation (PMA) in patients with pulmonary tuberculosis (TB), the processes underlying PMA and consequences for cytokine responses.In a cross-sectional study involving 65 Tanzanian TB patients in different phases of treatment and 29 healthy controls, TB patients had a significantly higher PMA. This increased PMA in TB patients was associated with increased monocyte CCR5, CD16 expression and PF4, but not with increased membrane-expressed or soluble P-selectin expression. These findings were confirmed in vitro: whereas incubation of whole blood with Mycobacterium tuberculosis (Mtb) did not activate platelets, monocytes became activated with higher CD11b, CD16 and CCR5 expression, but this was independent of platelet-monocyte interaction. Still, platelets had an anti-inflammatory effect on cytokine responses as peripheral blood mononuclear cells (PBMC) incubated with Mtb in the presence of platelets produced less interleukin (IL)-1β, tumor necrosis factor-α, IL-6 and interferon-γ and more IL-10.In conclusion, increased PMA during TB infection is caused by monocyte and not platelet activation. By counteracting the Mtb-induced pro-inflammatory leukocyte response, platelets may protect against excessive tissue damage, but may also compromise the production of protective cytokines, such as IFNƴ and TNFα.

Effects of anthocyanins and their gut metabolites on adenosine diphosphate-induced platelet activation and their aggregation with monocytes and neutrophils

Accumulating evidence suggests that anthocyanins play an important role in the cardioprotective effects associated with consumption of anthocyanin-rich foods. These benefits may partly be attributed to their effects on platelets, significant contributors to cardiovascular disease development. This study aimed to investigate the impact of physiologically relevant concentrations of anthocyanins and their metabolites on platelet activation and platelet-leukocyte aggregation.Whole blood from seven healthy volunteers was treated with anthocyanins: cyanidin-3-arabinoside, cyanidin-3-glucoside, cyanidin-3-galactoside, delphinidin-3-glucoside and peonidin-3-glucoside at 0.1 μM concentration or gut metabolites: 4-hydroxybenzaldehyde, protocatechuic, vanillic, ferulic and hippuric acids at 0.5 μM, 0.2 μM, 2 μM, 1 μM, 2 μM concentration, respectively. Markers of adenosine diphosphate-induced platelet activation (P-selectin and GPIIb-IIIa expression) and platelet-monocyte and platelet-neutrophil aggregation were analyzed using flow cytometry.Cyanidin-3-arabinoside, delphinidin-3-glucoside, and peonidin-3-glucoside decreased agonist-induced P-selectin expression, while cyanidin-3-galactoside and cyanidin-3-arabinoside reduced platelet-neutrophil aggregation. Hippuric and protocatechuic acids inhibited P-selectin expression, ferulic acid reduced platelet-monocyte aggregation, while 4-hydroxybenzaldehyde affected P-selectin expression, platelet-neutrophil and monocyte aggregation. Only cyanidin-3-glucoside and protocatechuic acid decreased GPIIb-IIIa expression.These results demonstrate the bioactivity of anthocyanins and their gut metabolites at physiologically relevant concentrations on platelet function and interaction with leukocytes, presenting mechanisms by which they contribute to the beneficial effects of habitual consumption of anthocyanin-rich foods on cardiovascular health.

Platelet-leucocyte aggregation is augmented in cirrhosis and further increased by platelet transfusion.

Thrombocytopenia and circulating dysfunctional immune cells are commonly observed in patients with cirrhosis. Platelets may form complexes with neutrophils, monocytes and T cells modulating their function. We recently reported increased frequencies of platelet-complexed neutrophils in cirrhosis with evidence of neutrophil activation upon contact with healthy platelets in vitro. Whether this occurs in vivo following platelet transfusion and contributes to systemic inflammation and endothelial activation is unknown. To characterise platelet-leucocyte aggregation in cirrhosis and to determine whether elective platelet transfusion results in perturbations associated with changes in markers of haemostasis, inflammation or endothelial activation. We collected blood from cirrhotics (n = 19) before and following elective platelet transfusion. We measured platelet-leucocyte aggregation, activation and function, and markers of platelet activation, systemic inflammation and endothelial activation by flow cytometry. Haemostasis was assessed by thromboelastometry and plasma haemostatic proteins. We observed a 2.5-fold increase in platelet-complexed neutrophils in patients with cirrhosis compared with healthy subjects and twofold more platelets attached per monocyte and T cell. All platelet-complexed leucocytes expressed higher levels of activation markers and platelet-complexed neutrophils had higher resting oxidative burst and phagocytic capacity than their nonplatelet-complexed counterparts (P < 0.001); most pronounced in patients with cirrhosis. Paradoxically, platelet-complexed leucocyte frequency decreased with increasing MELD score. Platelet transfusion increased soluble CD40 ligand (platelet activation marker), the frequency of platelet-complexed monocytes (P < 0.05) and improved haemostatic status. Cirrhotic patients have activated circulating platelet-complexed leucocytes with increased platelet-monocyte aggregation following elective platelet transfusion. Elective platelet transfusion might therefore exacerbate immune dysfunction in cirrhosis.

Reduced beta-amyloid sensitivity for platelet-monocyte aggregates in EDTA blood of alzheimer patients.

Alzheimer´s disease (AD) is a severe neurodegenerative brain disorder characterized by beta-amyloid plaques, Tau pathology, inflammation, neurodegeneration, and cerebrovascular dysfunction. Besides that, alterations in monocytes and platelets have been reported in the blood of Alzheimer patients. In the present study, we measured circulating levels of platelet-monocyte aggregates in EDTA blood of cognitively healthy participants and 40 AD patients, and examined their changes induced by stimulation with beta-amyloid peptides. We measured CD14, CD62P, and CD42a using fluorescence-activated cell scanning (FACS) analysis. Our data show that the levels of circulating monocyte-platelet aggregates were not different between healthy controls and AD patients. However, incubation with beta-amyloid-40, -42, and pyroglutamate-beta-amyloid increased the platelet-monocyte aggregation in healthy subjects, but not AD patients. Our data conclude that the interaction between monocytes and platelets is not altered in whole blood of AD patients, but their sensitivity toward beta-amyloid peptides is decreased. There might be a critical link between the interaction of platelets and monocytes in AD, which has to be explored in further studies.

Relationship between platelet-leukocyte aggregation and myocardial perfusion in patients with ST-segment elevation myocardial infarction after primary percutaneous coronary intervention

ObjectiveTo explore the relationship between inflammation, oxidative stress and poor myocardial perfusion in patients with acute ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention (PCI). BackgroundRisk factors and mechanisms of poor reperfusion in patients with STEMI after primary PCI remain unclear. MethodsA total of 143 patients who underwent primary PCI after STEMI were divided into good and poor perfusion groups according to sum-ST-segment resolution (sumSTR) and TIMI myocardial perfusion grade (TMP) results. Aortic sinus arterial blood was collected after primary PCI. The platelet-leukocyte aggregation (PLA), platelet-neutrophil aggregation (PNA), platelet-monocyte aggregation (PMA) and platelet-lymphocyte aggregation (PLyA) were measured by flow cytometry. The malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured by chemical colorimetry. ResultsThe leukocyte count, neutrophil ratio and high-sensitivity C-reactive protein were significantly higher in the poor perfusion group than the good perfusion group (p < 0.05). Multiple linear regression analysis showed that neutrophil ratio was an independent risk factor of sumSTR in STEMI patients after primary PCI (p < 0.01). The poor myocardial perfusion group had higher levels of PLA, PNA, PMA and MDA (p < 0.05). There were no differences in PLyA and SOD levels between the good and poor myocardial perfusion groups (p > 0.05). ConclusionInflammation and oxidative stress were related to poor myocardial perfusion in patients with STEMI after primary PCI.

Lack of effect of supplementation with EPA or DHA on platelet-monocyte aggregates and vascular function in healthy men

Background and AimsEicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) found in fish oil are postulated to have favourable effects on platelet, endothelial and vascular function. We investigated whether EPA has differential effects on in vivo platelet aggregation and other markers of cardiovascular risk compared to DHA. Methods and ResultsFollowing a 2 wk run-in taking encapsulated refined olive oil, 48 healthy young men were randomly allocated using a parallel design to receive EPA-rich (3.1 g EPA/d) or DHA-rich (2.9 g DHA/d) triglyceride concentrates or refined olive oil (placebo), for a total supplementary lipid intake of 5 g/d. The specified primary outcome was change in platelet monocyte aggregates (PMA); secondary outcomes were capillary density, augmentation index, digital pulse volume measurements, 24 h ambulatory BP, plasma 8-isoprostanes-F2α. Changes in the proportions of DHA and EPA in erythrocytes and non-esterified fatty acid composition indicated compliance to the intervention. There was no significant treatment effect on PMA (P = 0.382); mean changes (%) (95% CI) were placebo −0.5 (−2.0, 1.04), EPA 0.4 (−0.8, 1.6), DHA 0.3 (−1.5, 2.0). R-QUICKI, an index of insulin sensitivity, was greater following EPA compared to placebo (P < 0.05). No other significant differences were noted. ConclusionNeither EPA- nor DHA-rich fish oil supplementation influence platelet-monocyte aggregation or several markers of vascular function after 6 wk in healthy young males. This trial was registered at clinicaltrials.gov as NCT01735357.

Quantification of Shear-Induced Platelet Activation: High Shear Stresses for Short Exposure Time.

Thrombosis and thromboembolism are the life-threatening clinical complications for patients supported or treated with prosthetic cardiovascular devices. The high mechanical shear stress within these devices is believed to be the major contributing factor to cause platelet activation (PA) and function alteration, leading to thrombotic events. There have been limited quantitative data on how the high mechanical shear stress causes platelet activation. In this study, shear-induced PA in the ranges of well-defined shear stress and exposure time relevant to cardiovascular devices was quantitatively characterized for human blood using two novel flow-through Couette-type blood shearing devices. Four markers of platelet activation-surface P-selectin (CD62p), platelet-derived microparticles (PMPs), platelet-monocyte aggregation (PMA), and soluble P-selectin-were measured by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. The results indicated that PA induced by high shear stresses with short exposure time could be reliably detected with surface P-selectin, and, to a lesser extent, PMPs rather than soluble P-selectin. It was also verified that PMA can be a highly sensitive indirect marker of platelet activation. The quantitative relationship between percentage of activated platelets indicated by surface P-selectin expression and shear stress/exposure time follows well the power law functional form. The coefficients of the power law models of PA based on surface P-selectin expression were derived.

Reduced platelet hyperreactivity and platelet-monocyte aggregation in HIV-infected individuals receiving a raltegravir-based regimen.

Platelets are key cells in atherosclerosis and acute cardiovascular events. Platelet hyperreactivity and increased platelet-monocyte aggregation (PMA) are found in HIV-infected patients and may contribute to the excess cardiovascular risk. The integrase inhibitor raltegravir (RAL) has been associated with better residual viral suppression and reduction in inflammatory and coagulation biomarkers. The aim of our study was to investigate whether RAL-treated patients have reduced platelet reactivity and PMA. We performed a cross-sectional study involving 80 virologically suppressed adult HIV1-infected patients on a RAL-based (n = 25), nonnucleoside reverse transcriptase inhibitor (NNRTI)-based (n = 30) or a protease inhibitor based (n = 25) regimen and 30 healthy controls. Platelet reactivity was determined by measuring platelet P-selectin expression and the binding of fibrinogen to platelets to stimulation with two concentrations of ADP. PMA was determined by measuring the expression of the platelet marker CD42b on CD14 positive cells. HIV-infected individuals had higher platelet reactivity and PMA than controls. RAL-treated individuals showed significantly lower P-selectin expression to stimulation with low (P = 0.026 vs. NNRTI and P = 0.005 vs. protease inhibitor group) and high-dose ADP (P = 0.009 vs. NNRTI and P = 0.003 vs. protease inhibitor group). A similar trend for was found for fibrinogen binding, although only the difference in P-selectin expression between RAL and protease inhibitor treated patients reached statistical significance (P = 0.038). PMA was also lower in the RAL group than in the NNRTI (P = 0.037) and protease inhibitor (P = 0.034) groups. Use of a RAL-based regimen was associated with a reduction in persistent HIV-induced platelet hyperreactivity and PMA compared with NNRTI and protease inhibitor based regimen.

Effect of ω-3 fatty acid supplementation on endothelial function, endogenous fibrinolysis and platelet activation in patients with a previous myocardial infarction: a randomised controlled trial

ObjectiveThe mechanisms through which ω-3 fatty acids reduce adverse cardiac events remain uncertain. We aimed to investigate the effect of ω-3 fatty acid supplementation on endothelial vasomotor function, endogenous fibrinolysis,...

Cardiovascular effects of tumour necrosis factor α antagonism in patients with acute myocardial infarction: a first in human study

ObjectiveThe inflammatory cytokine, tumour necrosis factor α (TNF-α), exerts deleterious cardiovascular effects. We wished to determine the effects of TNF-α antagonism on endothelial function and platelet activation in patients with...