Microparticles and exercise in clinical populations

Microparticles (MPs) are shed membrane vesicles released from a variety of cell types in response to cellular activation or apoptosis. They are elevated in a wide variety of disease states and have been previously measured to assess both disease activity and severity. However, recent research suggests that they also possess bioeffector functions, including but not limited to promoting coagulation and thrombosis, inducing endothelial dysfunction, increasing pro‐inflammatory cytokine release and driving angiogenesis, thereby increasing cardiovascular risk. Current evidence suggests that exercise may reduce both the number and pathophysiological potential of circulating MPs, making them an attractive therapeutic target. However, the existing body of literature is largely comprised of in vitro or animal studies and thus drawing meaningful conclusions with regards to health and disease remains difficult. In this review, we highlight the role of microparticles in disease, comment on the use of exercise and dietary manipulation as a therapeutic strategy, and suggest future research directions that would serve to address some of the limitations present in the research to date

An increase in circulating monocyte and platelet derived microparticles during haemodialysis

An increase in circulating monocyte and platelet derived microparticles during haemodialysi

Microparticles and exercise in clinical populations

Microparticles (MPs) are shed membrane vesicles released from a variety of cell types in response to cellular activation or apoptosis. They are elevated in a wide variety of disease states and have been previously measured to assess both disease activity and severity. However, recent research suggests that they also possess bioeffector functions, including but not limited to promoting coagulation and thrombosis, inducing endothelial dysfunction, increasing pro‐inflammatory cytokine release and driving angiogenesis, thereby increasing cardiovascular risk. Current evidence suggests that exercise may reduce both the number and pathophysiological potential of circulating MPs, making them an attractive therapeutic target. However, the existing body of literature is largely comprised of in vitro or animal studies and thus drawing meaningful conclusions with regards to health and disease remains difficult. In this review, we highlight the role of microparticles in disease, comment on the use of exercise and dietary manipulation as a therapeutic strategy, and suggest future research directions that would serve to address some of the limitations present in the research to date

Microparticle responses to aerobic exercise and meal consumption in healthy men

PURPOSE: Microparticles (MPs) are shed extracellular vesicles that express the pro-thrombotic tissue factor (TF). Aerobic exercise may reduce MP count and TF expression. This study investigated the impact of acute running or rest followed by standardised meal consumption on MP phenotypes and TF expression. METHODS: 15 males (age: 22.9 ± 3.3 years; body mass: 81.9 ± 11.4 kg; V[Combining Dot Above]O2 max 54.9 ± 6.5 mL·kg·min; mean ± SD) completed 1h of running (70% V[Combining Dot Above]O2max) or rest at 9am, and consumed a standardised meal (1170 kcal, 43% CHO, 17% PRO, 40% fat) at 10:45am. Venous blood samples were taken at 9am, 10am and 11:30am. MP concentration, diameter, phenotypes and TF-expression were assessed using nanoparticle tracking analysis (NTA) and flow cytometry. RESULTS: NTA identified no changes in MP concentration or diameter in response to time or trial. Flow cytometry revealed total MP count increased from 9am to 10am (1.62 ± 2.28 to 1.74 ± 2.61 x10/L, p = .016, effect size (η) = .105), but was unaffected by trial. TF platelet-derived MP % reduced from 9am to 10am (44.0 ± 21.2 to 21.5 ± 9.3%, p = .001, η = .582) after exercise only (control: 36.8 ± 18.2 to 34.9 ± 11.9%, p = .972). TF neutrophil-derived MP % reduced from 9am to 11:30am (42.3 ± 17.2 to 25.1 ± 14.9%, p = 0.048, η = .801) in the exercise trial only (control: 28.5 ± 15.7 to 32.2 ± 9.6%, p = .508). CONCLUSION: Running induced a significant reduction in %TF platelet and neutrophil MP, suggesting a transient reduction in cardiovascular risk via reduced TF-stimulated thrombosis. This requires further investigation over longer time periods in cardiovascular disease populations

Influence of acute moderate- to high-intensity aerobic exercise on markers of immune function and microparticles in renal transplant recipients

Renal transplant recipients (RTRs) and non-dialysis chronic kidney disease (ND-CKD) patients display elevated circulating microparticle (MP) counts, whilst RTRs display immunosuppression-induced infection susceptibility. The impact of aerobic exercise on circulating immune cells and microparticles is unknown in RTRs. Fifteen RTRs (age 52.8±14.5 years, estimated glomerular filtration rate [eGFR] 51.7±19.8 ml/min/1.73m2 [mean ± SD]), 16 ND-CKD patients (54. ± 6.3 years, eGFR 61.9±21.0 ml/min/1.73m2, acting as a uremic control group), and 16 HCs (52.2±16.2 years, eGFR 85.6±6.1 ml/min/1.73m2) completed 20 minutes of walking at 60-70% VO2 peak. Venous blood samples were taken pre, post, and 1h post-exercise. Leukocytes and MPs were assessed using flow cytometry. Exercise increased classical (p = 0.001) and non-classical (p = 0.002) monocyte subset proportions but decreased the intermediate subset (p < 0.001) in all groups. Exercise also decreased the percentage of platelet-derived MPs that expressed tissue factor (TF+) in all groups (p = 0.01), though no other exercise-dependent effects were observed. The exercise-induced reduction in intermediate monocyte percentage suggests an anti-inflammatory effect, though this requires further investigation. The reduction in the percentage of TF+ platelet-derived MPs suggests reduced pro-thrombotic potential, though further functional assays are required. Exercise did not cause aberrant immune cell activation, suggesting its safety from an immunological standpoint (ISRCTN38935454)

The Effect of Resistance Exercise on Inflammatory and Myogenic Markers in Patients with Chronic Kidney Disease

Background: Muscle wasting is a common complication of Chronic Kidney Disease (CKD) and is clinically important given its strong association with morbidity and mortality in many other chronic conditions. Exercise provides physiological benefits for CKD patients, however the molecular response to exercise remains to be fully determined. We investigated the inflammatory and molecular response to resistance exercise before and after training in these patients. Methods: This is a secondary analysis of a randomized trial that investigated the effect of 8 week progressive resistance training on muscle mass and strength compared to non-exercising controls. A sub-set of the cohort consented to vastus lateralis skeletal muscle biopsies (n = 10 exercise, n = 7 control) in which the inflammatory response (IL-6, IL-15, MCP-1 TNF-α), myogenic (MyoD, myogenin, myostatin), anabolic (P-Akt, P-eEf2) and catabolic events (MuRF-1, MAFbx, 14 kDa, ubiquitin conjugates) and overall levels of oxidative stress have been studied. Results: A large inflammatory response to unaccustomed exercise was seen with IL-6, MCP-1, and TNF-α all significantly elevated from baseline by 53-fold (P < 0.001), 25-fold (P < 0.001), and 4-fold (P < 0.001), respectively. This response was reduced following training with IL-6, MCP-1, and TNF-α elevated non-significantly by 2-fold (P = 0.46), 2.4-fold (P = 0.19), and 2.5-fold (P = 0.06), respectively. In the untrained condition, an acute bout of resistance exercise did not result in increased phosphorylation of Akt (P = 0.84), but this was restored following training (P = 0.01). Neither unaccustomed nor accustomed exercise resulted in a change in myogenin or MyoD mRNA expression (P = 0.88, P = 0.90, respectively). There was no evidence that resistance exercise training created a prolonged oxidative stress response within the muscle, or increased catabolism. Conclusions: Unaccustomed exercise creates a large inflammatory response within the muscle, which is no longer present following a period of training. This indicates that resistance exercise does not provoke a detrimental on-going inflammatory response within the muscle

The influence of acute moderate-to-high intensity aerobic exercise on markers of immune function and microparticles in renal transplant recipients.

Renal transplant recipients (RTRs) and non-dialysis chronic kidney disease (ND-CKD) patients display elevated circulating microparticle (MP) counts, whilst RTRs display immunosuppression-induced infection susceptibility. The impact of aerobic exercise on circulating immune cells and microparticles is unknown in RTRs. Fifteen RTRs (age 52.8±14.5 years, estimated glomerular filtration rate [eGFR] 51.7±19.8 ml/min/1.73m2 [mean ± SD]), 16 ND-CKD patients (54. ± 6.3 years, eGFR 61.9±21.0 ml/min/1.73m2, acting as a uremic control group), and 16 HCs (52.2±16.2 years, eGFR 85.6±6.1 ml/min/1.73m2) completed 20 minutes of walking at 60-70% VO2 peak. Venous blood samples were taken pre, post, and 1h post-exercise. Leukocytes and MPs were assessed using flow cytometry. Exercise increased classical (p = 0.001) and non-classical (p = 0.002) monocyte subset proportions but decreased the intermediate subset (p < 0.001) in all groups. Exercise also decreased the percentage of platelet-derived MPs that expressed tissue factor (TF+) in all groups (p = 0.01), though no other exercise-dependent effects were observed. The exercise-induced reduction in intermediate monocyte percentage suggests an anti-inflammatory effect, though this requires further investigation. The reduction in the percentage of TF+ platelet-derived MPs suggests reduced pro-thrombotic potential, though further functional assays are required. Exercise did not cause aberrant immune cell activation, suggesting its safety from an immunological standpoint (ISRCTN38935454)

Additional file 1: of Does intensive management improve remission rates in patients with intermediate rheumatoid arthritis? (the TITRATE trial): study protocol for a randomised controlled trial

SPIRIT Checklist figure. (PPTX 333 kb

Intradialytic cycling does not exacerbate microparticles or circulating markers of systemic inflammation in haemodialysis patients

PurposePatients receiving haemodialysis (HD) display elevated circulating microparticle (MP) concentration, tissue factor (TF) expression and markers of systemic inflammation, though regular intradialytic cycling (IDC) may have a therapeutic effect. This study investigated the impact of regular, moderate-intensity IDC on circulating MPs and inflammatory markers in unit-based HD patients.MethodsPatients were cluster-randomised to intervention (n = 20, age: 51.4 ± 18.1 years, body mass: 77.6 ± 18.3 kg, mean ± SD) or no-exercise control (n = 20, 56.8 ± 14.0 years, 80.5 ± 26.5 kg). Intervention participants completed 30 min of moderate intensity (rating of perceived exertion [RPE] of 12–14) IDC, thrice weekly for 6 months. Pre-dialysis venous blood samples were obtained at 0, 3 and 6 months. Circulating MP phenotypes, cytokines, chemokine and MP TF expression were quantified using flow cytometry and cytometric bead array assays.ResultsDespite high exercise compliance (82%), no IDC-dependent effects were observed for any MP, cytokine or chemokine measure (p ≥ 0.051, ηρ2 ≤ 0.399) other than TNF-α (p = 0.001, ηρ2 = 0.186), though no significance was revealed upon post hoc analysis.ConclusionSix months of regular, moderate-intensity IDC had no effect on MPs, cytokines or chemokines. This suggests that the exercise did not exacerbate thrombotic or inflammatory status, though further functional assays are required to confirm this.Trial registrationISRCTN1129707, prospectively registered on 05/03/2015.</div

ASL data IDP summaries.

A) Grey matter mean CBF perfusion (ml/100g/min) measurements for the single post-label delay (PLD) sequence used across all sites. B) Grey matter mean CBF perfusion measurements for the multi-PLD sequence available only on the Siemens sites. Raw data is plotted to the left; the cross-site correlation matrices to the right (upper triangle, Pearson’s correlation; lower triangle, Spearman’s correlation).</p