Arterial function in response to a 50 km ultramarathon in recreational athletes.

This study was performed to determine whether prolonged endurance running results in acute endothelial dysfunction and wave-reflection, as endothelial dysfunction and arterial stiffness are cardiovascular risk factors. Vascular function (conduit artery/macrovascular and resistance artery/microvascular) was assessed in 11 experienced runners (8 males, 3 females) before, during and after a 50 km ultramarathon. Blood pressure (BP), heart rate (HR), wave reflection, augmentation index (AIx) and AIx corrected for HR (AIx75) were taken at all time points-Baseline (BL), following 10, 20, 30 and 40 km, 1 h post-completion (1HP) and 24 h post-completion (24HP). Flow-mediated dilatation (FMD) and inflammatory biomarkers were examined at BL, 1HP and 24HP. Reactive hyperaemia area under the curve (AUC) and shear rate AUC to peak dilatation were lower (∼75%) at 1HP compared with BL (P < 0.001 for both) and reactive hyperaemia was higher at 24HP (∼27%) compared with BL (P = 0.018). Compared to BL, both mean central systolic BP and mean central diastolic BP were 7% and 10% higher, respectively, following 10 km and 6% and 9% higher, respectively, following 20 km, and then decreased by 5% and 8%, respectively, at 24HP (P < 0.05 for all). AIx (%) decreased following 20 km and following 40 km compared with BL (P < 0.05 for both) but increased following 40 km when corrected for HR (AIx75) compared with BL (P = 0.02). Forward wave amplitude significantly increased at 10 km (15%) compared with BL (P = 0.049), whereas backward wave reflection and reflected magnitude were similar at all time points. FMD and baseline diameter remained similar. These data indicate preservation of macrovascular (endothelial) function, but not microvascular function resulting from the 50 km ultramarathon.

Influence of cardiorespiratory fitness and body composition on resting and post-exercise indices of vascular health in young adults.

Poor cardiorespiratory fitness may mediate vascular impairments at rest and following an acute bout of exercise in young healthy individuals. This study aimed to compare flow mediated dilation (FMD) and vascular augmentation index (AIx75) between young adults with low, moderate, and high levels of cardiorespiratory fitness before and after an acute bout of aerobic exercise. Forty-three participants (22 men; 21 women) between 18 and 29 years of age completed the study. Participants were classified into low, moderate, and high health-related cardiorespiratory fitness groups according to age- and sex-based relative maximal oxygen consumption (V˙O2 max) percentile rankings. FMD was performed using Doppler ultrasound and AIx75 was performed using pulse wave analysis at baseline and 60-min after a 30-min bout of treadmill running at 70% V˙O2 max. A significant interaction (p â€‹= â€‹0.047; ηp2 â€‹= â€‹0.142) was observed, with the moderate fitness group exhibiting a higher FMD post-exercise compared with baseline ([6.7% â€‹± â€‹3.1%] vs. [8.5% â€‹± â€‹2.8%], p â€‹= â€‹0.028; d â€‹= â€‹0.598). We found a significant main effect of group for AIx75 (p â€‹= â€‹0.023; ηp2 â€‹= â€‹0.168), with the high fitness group exhibiting lower AIx75 compared to low fitness group ([-10% â€‹± â€‹10%] vs. [2% â€‹± â€‹10%], respectively, p â€‹= â€‹0.019; g â€‹= â€‹1.07). This was eliminated after covarying for body fat percentage (p â€‹= â€‹0.489). Our findings suggest that resting FMD and AIx75 responses are not significantly influenced by cardiorespiratory fitness, but FMD recovery responses to exercise may be enhanced in individuals with moderate cardiorespiratory fitness levels.

Comparison of skeletal muscle oxidative function in young, middle-aged, and older males and females with similar physical activity levels.

Optimal skeletal muscle oxidative function (microvascular reactivity and mitochondrial capacity) is an integral part of healthy aging and is related to physical function and quality of life. We aimed to extend upon the understanding of skeletal muscle oxidative function with healthy aging in males and females across the adult life span. Younger (N = 22; 11 males), middle-aged (N = 19; 10 males), and older (N = 21; 10 males) adults completed this study. Time spent in moderate and vigorous physical activity was self-reported and similar among groups. Near-infrared spectroscopy was used to investigate skeletal muscle microvascular reperfusion [oxyhemoglobin-myoglobin (O2Hb+Mb) half-time to peak hyperemia (T½)], mitochondrial capacity [muscle oxygen consumption (mV̇o2) recovery rate constant], and walking tissue oxygen saturation ([Formula: see text]) of the tibialis anterior (TA) muscle at seven incremental walking speeds. Mitochondrial capacity was not significantly different across groups (P = 0.07). Younger adults exhibited significantly slower T½ compared with older adults (P = 0.006) and middle-aged adults (P = 0.025). There were no observed sex differences for mitochondrial capacity (P = 0.442) or T½ (P = 0.402). Older adults exhibited significantly lower [Formula: see text] across all walking speeds compared with younger adults (P = 0.003). Mitochondrial capacity and microvascular reperfusion are maintained in middle and older age, with no sex differences in either outcome. However, in older adults whole body functional movement, such as walking, may place an additional demand on the TA as a compensatory response to lower functional reserve not evident in distinct measures of mitochondrial capacity and microvascular reperfusion.NEW & NOTEWORTHY Compared with younger adults, mitochondrial capacity and microvascular reperfusion of the tibialis anterior (TA) muscle are well maintained in similarly physically active middle-aged and older adults, with no sex differences observed in either outcome. However, greater tissue oxygen utilization in older adults during walking highlights how whole body functional movement may place an additional demand on the TA that reveals a potential compensatory response to lower functional reserve not evident in distinct measures of mitochondrial capacity and microvascular reperfusion.

Muscle thickness and inflammation during a 50km ultramarathon in recreational runners.

PURPOSE: This study examined changes in circulating levels of inflammatory cytokines [IL-6, sIL-6R, TNF-α, and calprotectin], skeletal muscle morphology, and muscle strength following a 50km race in non-elite athletes. METHODS: Eleven individuals (8 men; 3 women) underwent pre-race assessments of rectus femoris muscle thickness (resting and contracted) using ultrasound, isometric knee extensor torque, and plasma cytokines. Measures were repeated after 10km of running, the 50km finish (post-race), and again 24-hrs post-race. RESULTS: Compared with baseline values, Δ muscle thickness (resting to contracted) increased significantly 24 hrs post-race (11 ± 11% vs. 22 ± 8%; P = 0.01). Knee extensor torque was significantly reduced immediately post-race (151 ± 46 vs. 134 ± 43 Nm; P = 0.047) but remained similar to post-race values at 24 hrs post-race (P = 0.613). Compared with pre-race levels, IL-6 and calprotectin concentrations increased 302% and 50% after 10km, respectively (P<0.017 for both), peaked post-race (2598% vs. pre-race for IL-6 and 68% vs. pre-race for calprotectin; P = 0.018 for both), and returned to pre-race levels at 24-hrs post-race (P>0.05 for both). Creatine kinase levels rose steadily during and after the race, peaking 24-hrs post-race (184 ± 113 U/L pre-race vs. 1508 ± 1815 U/L 24-hrs post-race; P = 0.005). CONCLUSION: This is the first report of delayed increases in Δ muscle thickness at 24 hrs post-50km, which are preceded by reductions in knee extensor torque and elevations in plasma IL-6, and calprotectin. Recreational athletes should consider the acute muscle inflammatory response when determining training and recovery strategies for 50km participation.

High-intensity functional exercise does not cause persistent elevations in augmentation index in young men and women.

Elevations in central augmentation index (AIx) are predictive of cardiovascular disease. The objective of this study was to examine AIx immediately and 24 h following an acute bout of high-intensity functional training (HIFT) in apparently healthy young adults. A second aim compared the exercise-induced AIx recovery response between men and women. Thirty-two recreationally active younger adults (n = 16 men) were tested. Baseline central hemodynamic measures were assessed, followed by a single bout of bodyweight HIFT. The HIFT included 4 rounds of burpees, jump squats, split squats, and walking lunges. Assessments were repeated 5, 10, 15, and 24 h post-exercise. AIx was normalized to a heart rate of 75 bpm (AIx75). There was a significant main effect of time on AIx75 across all groups (P < 0.001) with AIx75 increasing at all acute time points compared with baseline and returning to resting values 24 h post-exercise. When examining sex differences after covarying for height and body fat percentage, the authors found no time × sex interaction (P = 0.62), or main effect for sex (P = 0.41), but the significant main effect of time remained (P < 0.001). The AIx75 response to HIFT follows a similar recovery pattern as previously studied modes of exercise with no residual effects 24 h later and no differences between men and women indicating no persistent cardiovascular strain in younger adults participating in this mode of exercise.

CD31+ Circulating Angiogenic Cell Number and Subtypes are Reduced in Individuals with Chronic Stroke.

BACKGROUND AND PURPOSE: Reduced number and function of CD31+ circulating angiogenic cells (CACs) may explain vascular complications associated with the chronic phase stroke. The purpose of this study was to quantify CD31+ CAC paracrine function, total number and number of various subtypes of CD31+ CACs in individuals with chronic stroke compared with controls. METHODS: Peripheral blood mononuclear cells were isolated from chronic stroke participants and controls. CD31+ cells were quantified by flow cytometry, as was co-expression of CD31 in combination with CD14, CD3, CD11b, or CD34. Immunomagnetically selected CD31+ cells were cultured, and conditioned medium was used in a capillary-like network assay. RESULTS: Significantly lower levels of CD31+ CACs were found in stroke participants compared with controls (-24%; P=0.04). Additionally, CD31+/CD14+, CD31+/CD11b+ and CD31+/CD3+ cells were significantly lower in the chronic stroke group compared with controls (-45%, P=0.02; -47%, P=0.02 and -32%, P=0.03, respectively). There was no group effect on CD31+ CAC conditioned media-mediated capillary-like network formation. CONCLUSION: CD31+ CACs and subtypes may serve as potential therapeutic targets in chronic stroke recovery.

Circulating microparticle concentrations across acute and chronic cardiovascular disease conditions.

Concentrations of different circulating microparticles (MPs) may have clinical and physiological relevance to cardiovascular disease pathologies. PURPOSE: To quantify plasma concentrations of CD31+/CD42b-, CD62E+, and CD34+ MPs across healthy individuals and those with coronary artery disease (CAD) or acute cardiovascular events (non-ST elevation myocardial infarction (NSTEMI)). Fasted blood was obtained from CAD patients (n = 10), NSTEMI patients (n = 13), and healthy older men (n = 15) 60-75 years old. METHODS: CD31+/CD42b-, CD62E+, and CD34+ MPs were isolated from plasma and quantified using flow cytometry. Relationships between MP subtypes, fasting blood lipids, blood glucose, blood pressure, body mass index, and total number of medications were assessed. RESULTS: Concentrations of CD31+/CD42b- MPs were significantly lower in CAD and NSTEMI subjects compared with healthy individuals (p = .02 and .003, respectively). No differences between groups were found for CD62E+ or CD34+ MPs (p > .05 for both). Surprisingly, among all variables assessed, only CD62E+ MP concentrations were positively correlated with triglyceride levels (p = .012) and inversely correlated with SBP (p = .03). CONCLUSIONS: Our findings provide support for the use of different MP subtypes, specifically CD31+/CD42b- MPs, as a potential biomarker of cardiovascular disease. Importantly, results from this study should be looked at in adjunct to previous MP work in CVD conditions as a way of highlighting the complex interactions of variables such as comorbid conditions and medications on MP concentrations.

Sex-specific alterations in blood-borne factors in physically inactive individuals are detrimental to endothelial cell functions.

Mechanisms underlying the protective effects of both habitual endurance exercise and the female sex on vascular function are incompletely understood. Blood-borne circulating factors, such as circulating microRNAs (ci-miRs), may partially explain these effects. Blood samples were obtained from young, healthy men and women who either habitually performed endurance exercise (endurance trained) or were relatively inactive (sedentary). Women were tested during the early follicular phase of the menstrual cycle or the placebo pill phase of oral contraceptive to control for estrogen. Cultured human umbilical vein endothelial cells (HUVECs) were exposed to participants' serum in migration, proliferation, and reactive oxygen species (ROS) assays. Real-time quantitative polymerase chain reaction was used to quantify an initial array of 84 cardiovascular disease (CVD)-related ci-miRs, followed by validation of 10 ci-miRs. All participants were devoid of traditional CVD risk factors, and circulating estradiol concentration was not different between groups. Serum of endurance-trained women induced greater HUVEC migration compared with serum of sedentary women. HUVEC ROS production was greater in response to serum of sedentary men compared with serum of endurance-trained men and sedentary women. There were sex effects on the levels of nine ci-miRs, with greater levels in men, while ci-miRs-140-5p and 145-5p were also higher in sedentary compared with endurance-trained men and/or women. In a sex-specific manner, habitual endurance exercise was associated with beneficial effects of serum on HUVECs. Thus, alterations in circulating factors may contribute to the protective effects of habitual endurance exercise on vascular health. Additionally, sex had a greater impact than habitual activity level on the levels of vascular-related ci-miRs.NEW & NOTEWORTHY Serum from sedentary women caused impaired endothelial migration, whereas serum from sedentary men elicited increased endothelial reactive oxygen species production as compared with serum from their endurance-trained counterparts. Select CVD-related circulating microRNAs (ci-miRs) were higher in men than women, while ci-miRs-140-5p and 145-5p were also higher in sedentary versus trained men and/or women. Our data suggest that alterations in circulating factors may contribute to the protective effects of habitual exercise and sex on vascular health.

Sitting decreases endothelial microparticles but not circulating angiogenic cells irrespective of lower leg exercises: a randomized cross-over trial.

NEW FINDINGS: What is the central question of this study? What are the cellular and molecular determinants of increased risk for cardiovascular disease from prolonged sitting? What is the main finding and its importance? Prolonged sitting, independent of calf raise interruption strategies, decreases microparticle counts linked to endothelial activation and apoptosis. An acute bout of prolonged sitting appears to promote paradoxical decreases in microparticle counts, but the implications are not yet clear. ABSTRACT: Repeated exposure to prolonged sitting increases the risk for cardiovascular disease. However, the cellular links by which repeated exposure to prolonged sitting lead to increased cardiovascular risk have not been fully elucidated, with markers of vascular damage and repair such as microparticles (MPs) and circulating angiogenic cell (CACs) being promising targets. The objective of the study was to examine the effects of 3 h of sitting with or without intermittent calf raises on annexin V+ /CD34+ , annexin V+ /CD62E+ , and annexin V+ /CD31+ /42b- MP populations linked to CAC paracrine activity, endothelial activation and apoptosis, respectively, as well as CD14+ /31+ , CD3+ /31+ , and CD34+ CACs, which are linked to endothelial repair. In a random order, 20 sedentary participants (14 females, 22 ± 3 years) remained seated for 180 min with or without performing 10 calf raises every 10 min. Blood samples were obtained after 20 min of quiet rest in the supine position before and after sitting. Overall, sitting decreased annexin V+ /CD34+ MPs (-12 ± 5 events µl-1 , P < 0.01), annexin V+ /CD62E+ MPs (-17 ± 4 events µl-1 , P < 0.001), and annexin V+ /CD31+ /42b- MPs (-22 ± 6 events µl-1 , P < 0.001) regardless of condition. There were no differences in endothelin-1 plasma concentration, CD14+ /31+ , CD34+ or CD3+ /31+ CAC frequencies. Sitting did not alter CAC number, but decreased MPs linked to endothelial activation, apoptosis and CAC paracrine activity in a manner that was independent of muscle contraction. These findings support changes in markers of endothelial activation and apoptosis with sedentary behaviour and provide new insights into altered intercellular communication with physical inactivity such as prolonged sitting.

Serum IL-6 and sIL-6R in type 2 diabetes contribute to impaired capillary-like network formation.

We hypothesized that the serum from individuals with type 2 diabetes mellitus (T2DM) and impaired glucose tolerance (IGT) would reduce in vitro capillary-like network formation compared with normal glucose tolerance (NGT) serum and that this would occur along with higher serum concentrations of inflammatory cytokines and lower concentrations of angiogenic growth factors. Subjects were sedentary, older (55-65 yr) adults with NGT, IGT, or T2DM (n = 10/group) matched for body mass index. Human retroviral telomerized endothelial cells (HRVT-ECs) or coronary artery endothelial cells (CECs) were used in a capillary-like network formation assay using endothelial basal medium supplemented with 7.5% serum. Quantification of HRVT-EC network length indicated that serum from the T2DM group resulted in 32 and 35% lower network formation than when using serum from the NGT and IGT groups, respectively (P < 0.05). Serum from T2DM subjects resulted in CEC network formation that was 11 and 8% lower than when using serum from NGT and IGT subjects, respectively (P < 0.05). Analysis of serum cytokines indicated that IL-6 was 41% and 49% higher in the IGT and T2DM groups, respectively, compared with the NGT group (P < 0.05) and there was a trend for higher soluble interleukin-6 receptor (sIL-6R; P = 0.06) and IL-8 (P = 0.08) in the T2DM serum compared with NGT. The use of recombinant IL-6 and sIL-6R at concentrations detected in the T2DM serum also reduced capillary network formation compared with NGT concentrations (P < 0.05). These results suggest that IL-6 and sIL-6R present in the serum of T2DM individuals impair in vitro endothelial cell function across different cell lines. Our findings may have implications for the microvascular complications associated with T2DM.NEW & NOTEWORTHY Higher concentrations of serum factors, specifically Interleukin-6 and its soluble receptor found in individuals with type 2 diabetes (T2DM) appear to impair endothelial cell capillary-like network formation compared with those present in serum from individuals with impaired glucose tolerance and normal glucose tolerance. This may have implications for the vascular complications associated with T2DM.

Exercise and Cardiovascular Progenitor Cells.

Autologous stem/progenitor cell-based methods to restore blood flow and function to ischemic tissues are clinically appealing for the substantial proportion of the population with cardiovascular diseases. Early preclinical and case studies established the therapeutic potential of autologous cell therapies for neovascularization in ischemic tissues. However, trials over the past ∼15 years reveal the benefits of such therapies to be much smaller than originally estimated and a definitive clinical benefit is yet to be established. Recently, there has been an emphasis on improving the number and function of cells [herein generally referred to as circulating angiogenic cells (CACs)] used for autologous cell therapies. CACs include of several subsets of circulating cells, including endothelial progenitor cells, with proangiogenic potential that is largely exerted through paracrine functions. As exercise is known to improve CV outcomes such as angiogenesis and endothelial function, much attention is being given to exercise to improve the number and function of CACs. Accordingly, there is a growing body of evidence that acute, short-term, and chronic exercise have beneficial effects on the number and function of different subsets of CACs. In particular, recent studies show that aerobic exercise training can increase the number of CACs in circulation and enhance the function of isolated CACs as assessed in ex vivo assays. This review summarizes the roles of different subsets of CACs and the effects of acute and chronic exercise on CAC number and function, with a focus on the number and paracrine function of circulating CD34+ cells, CD31+ cells, and CD62E+ cells. © 2019 American Physiological Society. Compr Physiol 9:767-797, 2019.

Effects of regular endurance exercise on GlycA: Combined analysis of 14 exercise interventions.

BACKGROUND AND AIMS: GlycA is a relatively new biomarker for inflammation as well as cardiometabolic disease risk. However, the effect of exercise on GlycA is largely unknown. Therefore, the purpose of this study was to examine the effects of regular exercise on the inflammatory marker GlycA across seven studies and 14 exercise interventions. METHODS: Nuclear magnetic resonance spectroscopy, specifically signal amplitudes originating from the N-acetyl methyl group protons of the N-acetylglucosamine residues on the glycan branches of glycoproteins, was used to quantify GlycA concentrations. GlycA was measured before and after completion of an exercise intervention in 1568 individuals across seven studies and 14 exercise interventions. Random effects inverse variance weighting models were used to pool effects across interventions. RESULTS: Combined analysis of unadjusted data showed that regular exercise significantly (p = 2 × 10-6) reduced plasma GlycA (-8.26 ±â€¯1.8 µmol/L). This reduction remained significant (-9.12 ±â€¯1.9 µmol/L, p = 1.22 × 10-6) following adjustment for age, sex, race, baseline BMI, and baseline GlycA. Changes in GlycA were correlated with changes in traditional inflammatory markers, C-reactive protein, interleukin-6, and fibrinogen, however, these correlations were relatively weak (range r: 0.21-0.38, p < 0.0001). CONCLUSIONS: Regular exercise significantly reduced plasma GlycA across 14 different exercise interventions despite differences in exercise programs and study populations. The current study provides a greater understanding of the use of exercise as a potential therapy for the reduction of systemic inflammation. Further research is needed to understand the mechanisms behind the exercise-related reductions in GlycA.

Type 2 diabetes and older age contribute to elevated plasma microparticle concentrations independent of chronic stroke.

NEW FINDINGS: What is the central question of this study? What is the effect of chronic stroke on circulating microparticle populations, accounting for potential effects of age and type 2 diabetes? What is the main finding and its importance? Elevated concentrations of CD31+ /CD42b- and CD62E+ microparticles appear to be driven by type 2 diabetes but not chronic stroke and are associated with fasting glucose and triglyceride levels. Older age results in elevations in CD62E+ and CD34+ microparticle concentrations. These microparticles have been proposed as potential targets for diagnosing, treating and identifying the clinical progression and complications of type 2 diabetes. ABSTRACT: The elevated circulating concentration of endothelial microparticles (MPs) may provide an index of the extent and nature of cellular damage in chronic stroke. The purpose of this study was to determine the circulating concentrations of CD31+ /CD42b- , CD62E+ and CD34+ MPs in chronic stroke subjects, focusing on the effects of chronic stroke by comparison with both older adults without a history of stroke but with type 2 diabetes mellitus (T2DM) and older and young healthy controls. Plasma from three groups of sedentary older (50-75 years) men and women (chronic stroke, T2DM or older healthy) as well as a group of younger (18-39 years) healthy controls was isolated from fasting blood, and CD31+ /CD42b- , CD62E+ and CD34+ MPs were quantified using flow cytometry (n = 17/group). Concentrations of CD31+ /CD42b- and CD62E+ MPs were higher in the T2DM group (P < 0.05), but not chronic stroke, compared to older and younger healthy adults. CD62E+ MP and CD34+ MP concentrations were elevated in the older compared to younger adults (P < 0.05 for both). Sub-analyses excluding chronic stroke subjects who were also diagnosed with diabetes [stroke (diabetes- )] revealed lower CD31+ /CD42b- (P < 0.05) and CD62E+ (P = 0.08) MPs in the stroke (diabetes- ) group compared to the T2DM group. CD31+ /CD42b- MP and CD62E+ MP concentrations were each associated with fasting glucose levels and CD31+ /CD42b- MPs also were associated with triglyceride levels. As MPs have been proposed as potential targets for diagnosing, treating and identifying the clinical progression of T2DM, our study provides further support for the use of CD31+ /CD42b- and CD62E+ MPs in the clinical progression of T2DM and associated vascular complications.

The Microvasculature and Skeletal Muscle Health in Aging.

Aging and aging-related declines in physical activity are associated with physical and metabolic impairments. Skeletal muscle capillarization is reduced in sedentary older adults, may contribute to impairments in skeletal muscle, and is modifiable by exercise training. This article examines the hypothesis that preservation of skeletal muscle capillarization is essential to maintain metabolism, fitness, and function with aging.

Laboratory and Match Physiological Data From an Elite Male Collegiate Soccer Athlete.

This study compared physiological data from an elite collegiate soccer player to those of his teammates over 2 seasons. The player of special interest (player A) was the winner of the MAC Hermann Trophy and was therefore considered the top player in National Collegiate Athletic Association (NCAA) division I soccer for each of the 2 seasons in which data were collected. Maximal oxygen consumption (V[Combining Dot Above]O2max) was measured during preseasons and heart rate (HR) was recorded during competitive matches. Polar Training Loads (PTL) were calculated using the Polar Team2 Pro (Polar USA) system based on time spent in HR zones. Player A had a lower V[Combining Dot Above]O2max than the team average in 2012 (56 vs. 61.5 ± 4.3 ml·kg·min) and a similar value in 2013 (54 vs. 56.9 ± 5.1 ml·kg·min). During matches, player A showed consistent significant differences from the team in percentage of time spent at 70-79% maximal heart rate (HRmax) (12.8 ± 5.5% vs. 10.1 ± 4.0%), 80-89% HRmax (54.3 ± 11.5% vs. 29.3 ± 6.8%), and 90-100% HRmax (23.1 ± 10.6% vs. 45.4 ± 8.5%). This led to a consistently lower PTL per minute accumulated by player A compared with his teammates (3.6 ± 0.4 vs. 4.4 ± 0.3), which may be beneficial over a season and may be related to his success. Thus, the ability to regulate moments of maximal exertion is useful in reducing training load and may be a characteristic of elite players, although whether our findings relate to differences in the playing style, position, or aerobic capacity of player A are unknown.

Investigating the extremes of the continuum of paracrine functions in CD34-/CD31+ CACs across diverse populations.

Paracrine function of circulating angiogenic cells (CACs) is thought to contribute to vascular maintenance. We previously identified S100A8 and S100A9 secreted from physically inactive individuals' CD34-/CD31+ CACs as negative regulators of capillary-like network formation. The purpose of this study was to investigate further the extremes of the continuum of CAC paracrine actions using two distinctly different groups representing "healthy" and "impaired" CAC function. We aimed to determine how capillary-like network formation in human umbilical vein endothelial cells (HUVECs) is affected by S100A8 and S100A9 in concentrations secreted by CACs from different ends of the health spectrum. CD34-/CD31+ CACs were isolated and cultured from 10 impaired function individuals defined as older (50-89 yr), non-ST-elevation myocardial infarction patients and 10 healthy individuals defined as younger (18-35 yr), healthy individuals, and conditioned media (CM) was generated. CM from the impaired function group's CACs significantly diminished network formation compared with CM from the healthy group (P < 0.05). We identified elevations in S100A8, S100A9, and S100A8/A9 in the CM from the impaired function group (P < 0.05). Pretreatment of HUVECs with inhibitors to a known S100A8 and S100A9 receptor, Toll-like receptor 4 (TLR4), but not receptor for advanced glycation end products, improved HUVEC network formation (P < 0.05) compared with CM alone in the impaired function conditions. Exposure of HUVECs to the TLR4 signaling inhibitor also blocked recombinant S100A8- and S100A9-mediated reductions in network formation. Collectively, the results suggest that the mechanisms behind impaired CAC CD34-/CD31+ CM-mediated reductions in capillary-like network formation involve secretion of S100A8 and S100A9 and binding of these proteins to TLR4 receptors on HUVECs. NEW & NOTEWORTHY: S100A8 and S100A9 proteins in concentrations secreted by CD34-/CD31+ circulating angiogenic cells (CACs) with impaired function reduce endothelial cell capillary-like network formation. These effects appear to be mediated by Toll-like receptor 4 and are absent with S100A8 and S100A9 in concentrations secreted by healthy CD34-/CD31+ CACs.

Short-term exercise training improves flow-mediated dilation and circulating angiogenic cell number in older sedentary adults.

Cardiovascular disease risk increases with age due, in part, to impaired endothelial function and decreased circulating angiogenic cell (CAC) number and function. We sought to determine if 10 days of aerobic exercise training improves endothelial function, CAC number, and intracellular redox balance in older sedentary adults. Eleven healthy subjects (4 men, 7 women), 61 ± 2 years of age participated in 60 min of aerobic exercise at 70% maximal oxygen consumption for 10 consecutive days while maintaining body weight. Before and after training, endothelial function was measured as flow-mediated dilation of the brachial artery and fasting blood was drawn to enumerate 3 CAC subtypes. Intracellular reactive oxygen species (ROS) and nitric oxide (NO) in CD34+ CACs were measured using fluorescent probes and reinforced via real-time quantitative polymerase chain reaction. Flow-mediated dilation improved significantly following training (10% ± 1.3% before vs. 16% ± 1.4% after training; P < 0.05). Likewise, CD34+/KDR+ number increased 104% and KDR+ number increased 151% (P < 0.05 for both), although CD34+ number was not significantly altered (P > 0.05). Intracellular NO and ROS levels in CD34+ CACs were not different after training (P > 0.05 for both). Messenger RNA expression of SOD1, endothelial nitric oxide synthase, and NADPH oxidase 2 and neutrophil cytosolic factor 1 in CD34+ CACs was not significantly altered with training (P > 0.05). In conclusion, 10 consecutive days of aerobic exercise increased flow-mediated dilation and CAC number in older, previously sedentary adults, but did not affect intracellular redox balance in CD34+ CACs. Overall, these data indicate that even short-term aerobic exercise training can have a significant impact on cardiovascular disease risk factors.

Exercise-induced endothelial progenitor cell mobilization is attenuated in impaired glucose tolerance and type 2 diabetes.

Circulating endothelial progenitor cells (EPCs) contribute to vascular homeostasis and are fewer in those with type 2 diabetes mellitus (T2DM) compared with normal glucose tolerance (NGT), suggesting a link between EPCs and T2DM-associated vasculopathies. The purpose of this study was to assess EPC number and mobilization by acute submaximal exercise in older adults with NGT, impaired glucose tolerance (IGT) or T2DM. We tested the hypothesis that EPC mobilization is lower in IGT compared with NGT and further reduced in older adults with T2DM. Forty-five older (50-75 yr of age) men and women with NGT (n = 18), IGT (n = 10), or T2DM (n = 17) were characterized and underwent submaximal aerobic exercise tests with blood sampling for enumeration of vascular endothelial growth factor receptor 2+ (VEGFR2+) cells, CD34+ hematopoetic progenitor cells, and CD34+/VEGFR2+ EPCs by flow cytometry before and after exercise. Basal EPC number was 65 and 61% lower in the IGT and T2DM groups, respectively, compared with the NGT group (P < 0.05). EPC number increased 23% after acute exercise in the NGT group (P < 0.01), but did not change in the IGT or T2DM groups. Before and after exercise, VEGFR2+ cell number was lower in a stepwise manner across the NGT, IGT, and T2DM groups (P < 0.05). Basal CD34+ cell number was lower in the IGT group compared with NGT (P < 0.05), but did not change after exercise in any group. These findings suggest a CD34+/VEGFR2+ EPC mobilization defect in IGT and T2DM that could play a role in the cardiovascular diseases and capillary rarefaction associated with insulin resistance.

Chronic endurance exercise affects paracrine action of CD31+ and CD34+ cells on endothelial tube formation.

We aimed to determine if chronic endurance-exercise habits affected redox status and paracrine function of CD34(+) and CD34(-)/CD31(+) circulating angiogenic cells (CACs). Subjects were healthy, nonsmoking men and women aged 18-35 yr and categorized by chronic physical activity habits. Blood was drawn from each subject for isolation and culture of CD34(+) and CD34(-)/CD31(+) CACs. No differences in redox status were found in any group across either cell type. Conditioned media (CM) was generated from the cultured CACs and used in an in vitro human umbilical vein endothelial cell-based tube assay. CM from CD34(+) cells from inactive individuals resulted in tube structures that were 29% shorter in length (P < 0.05) and 45% less complex (P < 0.05) than the endurance-trained group. CD34(-)/CD31(+) CM from inactive subjects resulted in tube structures that were 26% shorter in length (P < 0.05) and 42% less complex (P < 0.05) than endurance-trained individuals. Proteomics analyses identified S100A8 and S100A9 in the CM. S100A9 levels were 103% higher (P < 0.05) and S100A8 was 97% higher in the CD34(-)/CD31(+) CM of inactive subjects compared with their endurance-trained counterparts with no significant differences in either protein in the CM of CD34(+) CACs as a function of training status. Recombinant S100A8/A9 treatment at concentrations detected in inactive subjects' CD34(-)/CD31(+) CAC CM also reduced tube formation (P < 0.05). These findings are the first, to our knowledge, to demonstrate a differential paracrine role in CD34(+) and CD34(-)/CD31(+) CACs on tube formation as a function of chronic physical activity habits and identifies a differential secretion of S100A9 by CD34(-)/CD31(+) CACs due to habitual exercise.

Circulating angiogenic and inflammatory cytokine responses to acute aerobic exercise in trained and sedentary young men.

PURPOSE: Endurance exercise training can ameliorate many cardiovascular and metabolic disorders and attenuate responses to inflammatory stimuli. The purpose of this study was to determine whether the angiogenic and pro-inflammatory cytokine response to acute endurance exercise differs between endurance-trained and sedentary young men. METHODS: Ten endurance-trained and ten sedentary healthy young men performed 30 min of treadmill running at 75 % VO2max with blood sampling before and after exercise. Plasma concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, IL-6, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), placental growth factor (PlGF), and soluble VEGF receptor-1 (sFlt-1) were measured by multiplex ELISA. RESULTS: Acute exercise increased IL-6 by 165 % (P < 0.05), IL-8 by 32 % (P < 0.05), PlGF by ~16 % (P < 0.05), sFlt-1 by 36 % (P < 0.001), and tended to increase bFGF by ~25 % (P = 0.06) in main effects analyses. TNF-α and VEGF did not change significantly with exercise in either group. Contrary to our hypothesis, there were no significant differences in TNF-α, IL-6, VEGF, bFGF, PlGF, or sFlt-1 between groups before or after acute exercise; however, there was a tendency for IL-8 concentrations to be higher in endurance-trained subjects compared to sedentary subjects (P = 0.06). CONCLUSIONS: These results indicate that 30 min of treadmill running at 75 % VO2max produces a systemic angiogenic and inflammatory reaction, but endurance exercise training does not appear to significantly alter these responses in healthy young men.