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

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

Statistical results for SWI-derived IDPs.

In the top two panels, the left column shows data for 14 IDPs derived from T2* data and the right column shows data for 14 IDPs derived from QSM data. A) Distribution of log-transformed P-values from repeated measures ANOVA testing for a site effect on the mean value of individual IDPs in each class; the solid horizontal line represents the P-value equivalent to FDR = 5%. Green dots represent IDPs fitted to the ANOVA model including data from all four sites; orange dots represent P-values for each IDP fitted to the ANOVA including only data from the three Siemens sites (Cambridge, Oxford, Liverpool). There were more significant between-site differences in mean IDPs when the GE data from KCL were included in the analysis B) Swarm plots showing distribution of intra-class correlation coefficients (ICCs) for the same IDPs, estimated for each pair of all 4 sites (green points), and for each pair of the three Siemens sites (orange points). C) Each column represents finer-grained results for representative IDPs from each class of IDP: from left to right, T2* right pallidum, QSM right pallidum. Top row, plots of each IDP for 8 subjects (coloured lines) scanned at each of 4 sites (x-axis labels). Bottom row, correlations between each pair of sites for each IDP: upper triangle, Pearson’s correlations; lower triangle, Spearman’s correlations.</p

T1 images, inverse SNR and inverse CNR metrics across four sites.

A) Representative T1 images of the same subject scanned at each of 4 sites in the travelling heads study. B) left panel, plots of inverse signal-to-noise ratio (iSNR) for 8 subjects (coloured lines) scanned at each of 4 sites (x-axis labels); right panel, plots of inverse contrast-to-noise ratio (iCNR) for the same subjects and sites. The grey violin plots in both panels indicate the equivalent distributions of T1 iSNR and iCNR, respectively, in the UK Biobank reference dataset, using matched random sampling of N = 8 participants. Box and whiskers represent inter-quartile range and 95% confidence intervals respectively. The iSNR and iCNR metrics are comparable across Siemens sites (CAM = Cambridge, OXF = Oxford, LIV = Liverpool) and aligned with the UKB benchmark distribution. Both iSNR and iCNR are higher for the GE site (KCL = Kings College London) (P < 0.05), indicating lower SNR and CNR.</p