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BACKGROUND: Arduous military training frequently consists of prolonged physical activity, sleep disturbance, and stress that increases musculoskeletal injury risk and performance decrements. Inflammatory and oxidative stress responses have been reported in response to arduous training, but with inconsistencies across markers and with under-representation of women. The purpose of the current report was to measure circulating inflammation and oxidative stress responses to military training and to correlate biomarkers with subjective measures of stress and sleep quality as well as military fitness test performance. METHODS: Candidates undergoing the 10-week Marine Corps Officer Candidate School (OCS; 101 men; 62 women) were monitored, with demographic and questionnaire data collected, and blood drawn before and after OCS. Blood was analyzed for six markers of inflammation and three markers of oxidative stress. Associations between biomarkers and questionnaire and fitness test performance were tested. RESULTS: All measured inflammatory markers as well as plasma antioxidant capacity were elevated following OCS. The inflammatory increase was higher in women for several markers. Sleep disturbance and stress perception were associated with IL-6, IL-10 and CRP concentrations, suggesting that low sleep disturbance and stress perception were associated with low inflammatory load. Additionally, those with the highest inflammation at each time point performed worse on fitness tests than those with low inflammation. CONCLUSIONS: Following arduous military training, the circulating environment in a significant portion of officer candidates resembled chronic low-grade inflammation. This circulating inflammatory environment appeared worse with poor sleep, high stress perception, and poor fitness test performance, with utility observed for CRP, IL-6, and IL-10 as biomarkers of these responses. Since inflammation may contribute to musculoskeletal injury and performance decrements, minimizing chronic inflammation during military training should be explored.
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ABSTRACT: Baumgartner, NW, Belbis, MD, Kargl, C, Holmes, MJ, Gavin, TP, Hirai, DM, and Kao, S-C. Acute effects of high-intensity resistance exercise on recognition of relational memory, lactate, and serum and plasma brain-derived neurotrophic factor. J Strength Cond Res XX(X): 000-000, 2024-Acute aerobic exercise improves memory, but this phenomenon is understudied in response to resistance exercise (RE) despite evidence that RE-induced increases in lactate and brain-derived neurotrophic factor (BDNF) play mechanistic roles in memory performance. To determine the acute effect of RE on lactate, BDNF, and their associations with object and relational memory, blood lactate, and serum and plasma BDNF were taken from 36 adults (average age 23.64 ± 3.89 years; 18 woman) before and immediately after 42 minutes of high-intensity RE and a rest condition on counterbalanced days. Subjects then immediately studied a series of paired objects and completed object and relational recognition tasks. Results revealed a condition by trial interaction, previously studied objects were remembered less accurately following RE (d = 0.66) but recognition occurred faster (d = 0.28), indicating a speed-accuracy tradeoff following RE. There was no effect of either intervention on relational recognition performance. Lactate (d = 3.68) and serum BDNF (d = 0.74) increased following RE, whereas there was no time-related change in lactate and serum BDNF following rest. However, changes in lactate and BDNF did not predict any measures of object (rs < 0.25, ps > 0.16) or relation recognition (rs < 0.28, ps > 0.13). Collectively, these findings suggest that acute high-intensity RE selectively improves the processing speed of recognizing objects at the cost of less accurate recognition of previously studied objects. Furthermore, changes in object and relational memory performance are unlikely driven by acute increases in lactate or BDNF following high-intensity RE.
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INTRODUCTION: Overuse musculoskeletal injuries (MSKIs) remain a significant medical challenge in military personnel undergoing military training courses; a further understanding of the biological process leading to overuse MSKI development and biological signatures for injury risk are warranted. The purpose of this study was to determine the association between overuse MSKI occurrence and physiological characteristics of allostatic load (AL) characterized as maladaptive biological responses to chronic stress measured by wearable devices in US Marine Corps officer candidates during a 10-week training course. METHODS: Devices recorded energy expenditure (EE), daytime heart rate (HR), sleeping HR, and sleep architecture (time and percent of deep, light, REM sleep, awake time, total sleep). Flux was calculated as the raw or absolute difference in the average value for that day or night and the day or night beforehand. Linear mixed-effect model analysis accounting for cardiorespiratory fitness assessed the association between overuse MSKI occurrence and device metrics (α = 0.05). RESULTS: Sixty-nine participants (23 females) were included. Twenty-one participants (eight females) sustained an overuse MSKI. Overuse MSKI occurrence in male participants was positively associated with daytime HR (ß = 5.316, p = 0.008), sleeping HR (ß = 2.708, p = 0.032), relative EE (ß = 8.968, p = 0.001), absolute flux in relative EE (ß = 2.994, p = 0.002), absolute EE (ß = 626.830, p = 0.001), and absolute flux in absolute EE (ß = 204.062, p = 0.004). Overuse MSKI occurrence in female participants was positively associated with relative EE (ß = 5.955, p = 0.026), deep sleep time (ß = 0.664, p < 0.001), %deep sleep (ß = 12.564, p < 0.001) and negatively associated with absolute flux in sleeping HR (ß = -0.660, p = 0.009). CONCLUSIONS: Overuse MSKI occurrences were associated with physiological characteristics of AL including chronically elevated HR and EE and greater time in restorative sleep stages, which may serve as biological signatures for overuse MSKI risk.
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Concurrent resistance and endurance exercise training (CET) has well-studied benefits; however, inherent hormonal and genetic differences alter adaptive responses to exercise between sexes. Extracellular vesicles (EVs) are factors that contribute to adaptive signaling. Our purpose was to test if EV characteristics differ between men and women following CET. 18 young healthy participants underwent 12-weeks of CET. Prior to and following CET, subjects performed an acute bout of heavy resistance exercise (AHRET) consisting of 6 × 10 back squats at 75% 1RM. At rest and following AHRET, EVs were isolated from plasma and characteristics and miRNA contents were analyzed. AHRET elevated EV abundance in trained men only (+51%) and AHRET-induced changes were observed for muscle-derived EVs and microvesicles. There were considerable sex-specific effects of CET on EV miRNAs, highlighted by larger variation following the 12-week program in men compared to women at rest. Pathway analysis based on differentially expressed EV miRNAs predicted that AHRET and 12 weeks of CET in men positively regulates hypertrophy and growth pathways more so than in women. This report highlights sex-based differences in the EV response to resistance and concurrent exercise training and suggests that EVs may be important adaptive signaling factors altered by exercise training.
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Vesículas Extracelulares , MicroARNs , Entrenamiento de Fuerza , Humanos , Femenino , Masculino , Vesículas Extracelulares/metabolismo , Entrenamiento de Fuerza/métodos , Adulto , MicroARNs/sangre , MicroARNs/metabolismo , Adulto Joven , Ejercicio Físico/fisiología , Caracteres Sexuales , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiología , Entrenamiento Aeróbico/métodos , Factores SexualesRESUMEN
This study compared the structural and cellular skeletal muscle factors underpinning adaptations in maximal strength, power, aerobic capacity, and lean body mass to a 12-week concurrent resistance and interval training program in men and women. Recreationally active women and men completed three training sessions per week consisting of high-intensity, low-volume resistance training followed by interval training performed using a variety upper and lower body exercises representative of military occupational tasks. Pre- and post-training vastus lateralis muscle biopsies were analyzed for changes in muscle fiber type, cross-sectional area, capillarization, and mitochondrial biogenesis marker content. Changes in maximal strength, aerobic capacity, and lean body mass (LBM) were also assessed. Training elicited hypertrophy of type I (12.9%; p = 0.016) and type IIa (12.7%; p = 0.007) muscle fibers in men only. In both sexes, training decreased type IIx fiber expression (1.9%; p = 0.046) and increased total PGC-1α (29.7%, p < 0.001) and citrate synthase (11.0%; p < 0.014) content, but had no effect on COX IV content or muscle capillarization. In both sexes, training increased maximal strength and LBM but not aerobic capacity. The concurrent training program was effective at increasing strength and LBM but not at improving aerobic capacity or skeletal muscle adaptations underpinning aerobic performance.
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Músculo Esquelético , Entrenamiento de Fuerza , Masculino , Humanos , Femenino , Músculo Esquelético/metabolismo , Fibras Musculares Esqueléticas/fisiología , Músculo Cuádriceps , Ejercicio Físico/fisiología , Terapia por Ejercicio , Fuerza MuscularRESUMEN
Skeletal muscle fibers regulate surrounding endothelial cells (EC) via secretion of numerous angiogenic factors, including extracellular vesicles (SkM-EV). Muscle fibers are broadly classified as oxidative (OXI) or glycolytic (GLY) depending on their metabolic characteristics. OXI fibers secrete more pro-angiogenic factors and have greater capillary densities than GLY fibers. OXI muscle secretes more EV than GLY, however it is unknown whether muscle metabolic characteristics regulate EV contents and signaling potential. EVs were isolated from primarily oxidative or glycolytic muscle tissue from mice. MicroRNA (miR) contents were determined and endothelial cells were treated with OXI- and GLY-EV to investigate angiogenic signaling potential. There were considerable differences in miR contents between OXI- and GLY-EV and pathway analysis identified that OXI-EV miR were predicted to positively regulate multiple endothelial-specific pathways, compared to GLY-EV. OXI-EV improved in vitro angiogenesis, which may have been mediated through nitric oxide synthase (NOS) related pathways, as treatment of endothelial cells with a non-selective NOS inhibitor abolished the angiogenic benefits of OXI-EV. This is the first report to show widespread differences in miR contents between SkM-EV isolated from metabolically different muscle tissue and the first to demonstrate that oxidative muscle tissue secretes EV with greater angiogenic signaling potential than glycolytic muscle tissue.
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Vesículas Extracelulares , MicroARNs , Animales , Ratones , Células Endoteliales/metabolismo , Músculo Esquelético/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Vesículas Extracelulares/metabolismo , Estrés OxidativoRESUMEN
Exercise-induced skeletal muscle angiogenesis is a well-known physiological adaptation that occurs in humans in response to exercise training and can lead to endurance performance benefits, as well as improvements in cardiovascular and skeletal tissue health. An increase in capillary density in skeletal muscle improves diffusive oxygen exchange and waste extraction, and thus greater fatigue resistance, which has application to athletes but also to the general population. Exercise-induced angiogenesis can significantly contribute to improvements in cardiovascular and metabolic health, such as the increase in muscle glucose uptake, important for the prevention of diabetes. Recently, our understanding of the mechanisms by which angiogenesis occurs with exercise has grown substantially. This review will detail the biochemical, cellular and biomechanical signals for exercise-induced skeletal muscle angiogenesis, including recent work on extracellular vesicles and circulating angiogenic cells. In addition, the influence of age, sex, exercise intensity/duration, as well as recent observations with the use of blood flow restricted exercise, will also be discussed in detail. This review will provide academics and practitioners with mechanistic and applied evidence for optimising training interventions to promote physical performance through manipulating capillarisation in skeletal muscle.
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Ejercicio Físico , Músculo Esquelético , Humanos , Músculo Esquelético/fisiología , Ejercicio Físico/fisiología , Capilares , Hemodinámica , Neovascularización FisiológicaRESUMEN
Few noninvasive therapies currently exist to improve functional capacity in people with lower extremity peripheral artery disease (PAD). The goal of the present study was to test the hypothesis that unsupervised, home-based leg heat therapy (HT) using water-circulating trousers perfused with warm water would improve walking performance in patients with PAD. Patients with symptomatic PAD were randomized into either leg HT (n = 18) or a sham treatment (n = 16). Patients were provided with water-circulating trousers and a portable pump and were asked to apply the therapy daily (7 days/wk, 90 min/session) for 8 wk. The primary study outcome was the change from baseline in 6-min walk distance at 8-wk follow-up. Secondary outcomes included the claudication onset-time, peak walking time, peak pulmonary oxygen consumption and peak blood pressure during a graded treadmill test, resting blood pressure, the ankle-brachial index, postocclusive reactive hyperemia in the calf, cutaneous microvascular reactivity, and perceived quality of life. Of the 34 participants randomized, 29 completed the 8-wk follow-up. The change in 6-min walk distance at the 8-wk follow-up was significantly higher (P = 0.029) in the group exposed to HT than in the sham-treated group (Sham: median: -0.9; 25%, 75% percentiles: -5.8, 14.3; HT: median: 21.3; 25%, 75% percentiles: 10.1, 42.4, P = 0.029). There were no significant differences in secondary outcomes between the HT and sham group at 8-wk follow-up. The results of this pilot study indicate that unsupervised, home-based leg HT is safe, well-tolerated, and elicits a clinically meaningful improvement in walking tolerance in patients with symptomatic PAD.NEW & NOTEWORTHY This is the first sham-controlled trial to examine the effects of home-based leg heat therapy (HT) on walking performance in patients with peripheral artery disease (PAD). We demonstrate that unsupervised HT using water-circulating trousers is safe, well-tolerated, and elicits meaningful changes in walking ability in patients with symptomatic PAD. This home-based treatment option is practical, painless, and may be a feasible adjunctive therapy to counteract the decline in lower extremity physical function in patients with PAD.
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Enfermedad Arterial Periférica , Calidad de Vida , Calor , Humanos , Claudicación Intermitente/terapia , Pierna , Extremidad Inferior , Enfermedad Arterial Periférica/terapia , Proyectos Piloto , Caminata/fisiología , AguaRESUMEN
NEW FINDINGS: What is the central question of this study? Do obesity and acute resistance exercise alter the regulation of muscle intercellular communication pathways consistent with inadequate compensatory angiogenesis in response to muscle loading present in individuals with obesity? What is the main finding and its importance? Obesity is associated with differences in both pro- and anti-angiogenic signalling consistent with lower muscle capillarization. Acute resistance exercise increases the release of skeletal muscle small extracellular vesicles independent of body mass. These results identify new cellular factors associated with impaired angiogenesis in obesity and the positive effects of acute resistance exercise in lean and obese skeletal muscle. ABSTRACT: Obesity (OB) impairs cell-to-cell communication signalling. Small extracellular vesicles (EVs), which include exosomes, are released by skeletal muscle and participate in cell-to-cell communication, including the regulation of angiogenesis. Resistance exercise (REx) increases muscle fibre size and capillarization. Although obesity increases muscle fibre size, there is an inadequate increase in capillarization such that capillary density is reduced. It was hypothesized that REx-induced angiogenic signalling and EV biogenesis would be lower with obesity. Sedentary lean (LN) and OB subjects (n = 8 per group) performed three sets of single-leg knee-extension REx at 80% of maximum. Muscle biopsies were obtained at rest, 15 min and 3 h postexercise and analysed for angiogenic and EV biogenesis mRNA and protein. In OB subjects, muscle fibre size was â¼20% greater and capillary density with type II fibres â¼25% lower compared with LN subjects (P < 0.001). In response to REx, the increase in VEGF mRNA (pro-angiogenic) was similar (3-fold) between groups, while thrombospondin-1 (TSP-1) mRNA (anti-angiogenic) increased â¼2.5-fold in OB subjects only (P = 0.010). miR-130a (pro-angiogenic) was â¼1.4-fold (P = 0.011) and miR-503 (anti-angiogenic) â¼1.8-fold (P = 0.017) greater in OB compared with LN subjects at all time points. In both groups, acute REx decreased the EV surface protein Alix by â¼50%, consistent with the release of exosomes (P = 0.016). Acute REx appears to induce the release of skeletal muscle small EVs independent of body mass. However, with obesity there is predominantly impaired angiogenic signalling, consistent with inadequate angiogenesis in response to basal muscle hypertrophy.
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Músculo Esquelético , Neovascularización Fisiológica , Obesidad , Entrenamiento de Fuerza , Humanos , MicroARNs/metabolismo , Músculo Esquelético/fisiología , Obesidad/metabolismo , ARN Mensajero/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
NEW FINDINGS: What is the central question of this study? What is the impact of stress-induced premature senescence on skeletal muscle myoblast-derived extracellular vesicles (EVs) and myoblast-endothelial cell crosstalk? What is the main finding and its importance? Hydrogen peroxide treatment of human myoblasts induced stress-induced premature senescence (SIPS) and increased the release of exosome-sized EVs (30-150 nm in size) five-fold compared to untreated controls. Treatment of SIPS myoblast-derived EVs on endothelial cells increased senescence markers and decreased proliferation. Gene expression analysis of SIPS myoblast-derived EVs revealed a four-fold increase in senescence factor transforming growth factor-ß. These results highlight potential mechanisms by which senescence imparts deleterious effects on the cellular microenvironment. ABSTRACT: Cellular senescence contributes to numerous diseases through the release of pro-inflammatory factors as part of the senescence-associated secretory phenotype (SASP). In skeletal muscle, resident muscle progenitor cells (satellite cells) express markers of senescence with advancing age and in response to various pathologies, which contributes to reduced regenerative capacities in vitro. Satellite cells regulate their microenvironment in part through the release of extracellular vesicles (EVs), but the effect of senescence on EV signaling is unknown. Primary human myoblasts were isolated following biopsies of the vastus lateralis from young healthy subjects. Hydrogen peroxide (H2 O2 ) treatment was used to achieve stress-induced premature senescence (SIPS) of myoblasts. EVs secreted by myoblasts with and without H2 O2 treatment were isolated, analysed and used to treat human umbilical vein endothelial cells (HUVECs) to assess senescence and angiogenic impact. H2 O2 treatment of primary human myoblasts in vitro increased markers of senescence (ß-galactosidase and p21Cip1 ), decreased proliferation and increased exosome-like EV (30-150 nm) release approximately five-fold. In HUVECs, EV treatment from H2 O2 -treated myoblasts increased markers of senescence (ß-galactosidase and transforming growth factor ß), decreased proliferation and impaired HUVEC tube formation. Analysis of H2 O2 -treated myoblast-derived EV mRNA revealed a nearly four-fold increase in transforming growth factor ß expression. Our novel results highlight the impact of SIPS on myoblast communication and identify a VasoMyo Crosstalk by which SIPS myoblast-derived EVs impair endothelial cell function in vitro.
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Vesículas Extracelulares , Mioblastos Esqueléticos , Proliferación Celular , Senescencia Celular , Vesículas Extracelulares/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Mioblastos Esqueléticos/metabolismoRESUMEN
PURPOSE: To investigate the effects of a single session of either peristaltic pulse dynamic leg compressions (PPDC) or local heat therapy (HT) after prolonged intermittent shuttle running on skeletal muscle glycogen content, muscle function, and the expression of factors involved in skeletal muscle remodeling. METHODS: Twenty-six trained individuals were randomly allocated to either a PPDC (n = 13) or a HT (n = 13) group. After completing a 90-min session of intermittent shuttle running, participants consumed 0.3 g·kg-1 protein plus 1.0 g·kg-1 carbohydrate and received either PPDC or HT for 60 min in one randomly selected leg, while the opposite leg served as control. Muscle biopsies from both legs were obtained before and after exposure to the treatments. Muscle function and soreness were also evaluated before, immediately after, and 24 h after the exercise bout. RESULTS: The changes in glycogen content were similar (P > 0.05) between the thigh exposed to PPDC and the control thigh ~90 min (Control: 14.9 ± 34.3 vs PPDC: 29.6 ± 34 mmol·kg-1 wet wt) and ~210 min (Control: 45.8 ± 40.7 vs PPDC: 52 ± 25.3 mmol·kg-1 wet wt) after the treatment. There were also no differences in the change in glycogen content between thighs ~90 min (Control: 35.9 ± 26.1 vs HT: 38.7 ± 21.3 mmol·kg-1 wet wt) and ~210 min (Control: 61.4 ± 50.6 vs HT: 63.4 ± 17.5 mmol·kg-1 wet wt) after local HT. The changes in peak torque and fatigue resistance of the knee extensors, muscle soreness, and the mRNA expression and protein abundance of select factors were also similar (P > 0.05) in both thighs, irrespective of the treatment. CONCLUSIONS: A single 1-h session of either PPDC or local HT does not accelerate glycogen resynthesis and the recovery of muscle function after prolonged intermittent shuttle running.
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Glucógeno/biosíntesis , Calor/uso terapéutico , Aparatos de Compresión Neumática Intermitente , Músculo Esquelético/metabolismo , Carrera/fisiología , Adolescente , Adulto , Femenino , Humanos , Rodilla/fisiología , Masculino , Fatiga Muscular , Proteínas Musculares/metabolismo , Fuerza Muscular , Mialgia/terapia , ARN Mensajero/metabolismo , Torque , Adulto JovenAsunto(s)
Proteínas Musculares , Atrofia Muscular , Animales , Masaje , Músculo Esquelético , Proteolisis , RatasRESUMEN
KEY POINTS: Cellular communication occurs between endothelial cells and skeletal muscle satellite cells and is mitogenic for both cell types under normal conditions. Skeletal muscle atrophy and endothelial cell dysfunction occur in tandem in cardiovascular disease, type II diabetes and ageing. The present study investigated how induction of endothelial cell dysfunction via high glucose treatment impacts growth and differentiation of human skeletal muscle satellite cells in vitro. Secreted factors from high glucose treated endothelial cells impaired satellite cell expansion and differentiation via decreased proliferation and dysregulation of p38 mitogen-activated protein kinase in satellite cells committed to myogenesis. These findings highlight a novel potential role for endothelial cells in the development and pathology of skeletal muscle atrophy, which is common in patients with endothelial dysfunction related pathologies. ABSTRACT: Cross-talk between endothelial cells (ECs) and skeletal muscle satellite cells (MuSC) has been identified as an important regulator of cellular functions in both cell types. In healthy conditions, EC secreted factors promote MuSC growth and differentiation. Endothelial and satellite cell dysfunction occur in tandem in many disease states; however, no data exist examining the impact of dysfunctional EC signalling on satellite cells. Therefore, the present study aimed to evaluate the effect that factors secreted from high glucose (HG) treated ECs have on the growth and differentiation of human satellite cells (HMuSC) using a conditioned medium (CM) cell culture model. Satellite cells were isolated from human skeletal muscle and grown in CM from normal or HG treated human umbilical vein ECs (HUVECs). Satellite cells grown in CM from HG treated HUVECs reduced growth (25%), differentiation (25%) and myonuclear fusion (35%). These responses were associated with increased superoxide (50%) and inflammatory cytokines (25-50%) in HG treated HUVECs and HG-CM. Decreased expansion of HG-CM treated HMuSCs was driven by a decrease in proliferation. Impaired gene expression and protein content of myogenic differentiation factors were preceded by decreased phosphorylation of p38 mitogen-activated protein kinase in HMuSC treated with CM from HG treated HUVECs. The results obtained in the present study are the first to show that factors secreted from HG treated ECs cause impairments in human muscle satellite cell growth and differentiation in vitro, highlighting endothelial cell health and secretion as a potential target for treating vascular disease-associated skeletal muscle dysfunction.
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Glucosa/farmacología , Fibras Musculares Esqueléticas/efectos de los fármacos , Células Satélite del Músculo Esquelético/efectos de los fármacos , Adulto , Diferenciación Celular , Células Cultivadas , Femenino , Células Endoteliales de la Vena Umbilical Humana , Humanos , Masculino , Fibras Musculares Esqueléticas/fisiología , Células Satélite del Músculo Esquelético/fisiología , Adulto JovenRESUMEN
NEW FINDINGS: What is the central question of this study? Capillary rarefaction is found in diabetic and aged muscle, whereas exercise increases skeletal muscle angiogenesis. The association implies a crosstalk between muscle cells and endothelial cells. The underlying mechanisms mediating the crosstalk between these cells remains to be elucidated fully. What is the main finding and its importance? Endothelial cell functions are regulated by skeletal muscle cell-derived exosomes via a vascular endothelial growth factor-independent pathway. This study reveals a new mechanism mediating the crosstalk between skeletal muscle cells and endothelial cells. ABSTRACT: Loss of skeletal muscle capillarization, known as capillary rarefaction, is found in type 2 diabetes, chronic heart failure and healthy ageing and is associated with impaired delivery of substrates to the muscle. However, the interaction and communication of skeletal muscle with endothelial cells in the regulation of capillaries surrounding the muscle remains elusive. Exosomes are a type of secreted extracellular vesicle containing mRNAs, proteins and, especially, microRNAs that exert paracrine and endocrine effects. In this study, we investigated whether skeletal muscle-derived exosomes (SkM-Exo) regulate the endothelial cell functions of angiogenesis. We demonstrated that C2C12 myotube-derived exosomes improved endothelial cell functions, assessed by the proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs), which were increased by 20, 23 and 40%, respectively, after SkM-Exo exposure. The SkM-Exo failed to activate HUVEC vascular endothelial growth factor (VEGF) signalling. The SkM-Exo increased HUVEC reactive oxygen species and activated the nuclear factor-κB pathway, suggesting that SkM-Exo-induced angiogenesis was mediated by a VEGF-independent pathway. In addition, several angiogenic microRNAs were packaged in SkM-Exo, with miR-130a being particularly enriched and successfully transferred from SkM-Exo to HUVECs. Delivery of miRNAs into endothelial cells might explain the enhancement of reactive oxygen species production and angiogenesis by SkM-Exo. The potential angiogenic effect of SkM-Exo could provide an effective therapy for promoting skeletal muscle angiogenesis in diseases characterized by capillary rarefaction or inadequate angiogenesis.
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Exosomas/metabolismo , Exosomas/fisiología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/fisiología , FN-kappa B/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/fisiología , Animales , Línea Celular , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Diabetes Mellitus Tipo 2 , Humanos , Masculino , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/fisiología , Ratones , Ratones Endogámicos C57BL , MicroARNs/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/fisiología , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiología , Neovascularización Fisiológica/fisiología , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
ABSTRACT Objective The enzymatic activity of 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2) is key to protecting mineral corticoid receptors from cortisol and has been implicated in blood pressure regulation. Grapefruit juice (GFJ) and acidity are thought to inhibit this enzyme in vitro. This study examines the effect of GFJ and intense exercise on 11β-HSD2 enzyme activity in vivo. Subjects and methods Eighteen subjects ingested GFJ or apple juice (CON) on separate days prior to reporting to the laboratory in a randomized order. Saliva (Sal) samples were obtained at baseline, 15 and 45 minutes post-treadmill stress test; Sal cortisone (E) and cortisol (F) levels were determined, and the Sal cortisone:cortisol (E:F) ratio was used as an index of 11β-HSD2 enzyme activity at rest and after intense muscular work. Results GFJ treatment decreased baseline 11β-HSD2 enzyme activity (44%) and Sal-E (28%) compared to CON (both, p < 0.05). Sal-E (r = 0.61, p < 0.05) and Sal-F (r = 0.66, p < 0.05) were correlated with diastolic blood pressure (DBP) in GFJ-treated individuals. Treadmill stress significantly increased Sal-E and Sal-F but did not alter 11β-HSD2 enzyme activity regardless of treatment. When treatments were examined separately, CON 11β-HSD2 enzyme activity decreased by 36% (p < 0.05) from baseline to 15 post-treadmill exercise. Conclusion Our findings suggest that GFJ and intense muscular work decrease 11β-HSD-2 activity independently, and no additive effect was noted. The association between DBP and the levels of Sal-F and Sal-E during the GFJ trial should be interpreted cautiously and warrants further investigation.
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Humanos , Masculino , Femenino , Adulto , Cortisona/sangre , Músculo Esquelético/fisiología , Citrus paradisi , Esfuerzo Físico/fisiología , Jugos de Frutas y Vegetales/efectos adversos , Presión Sanguínea/fisiología , Estudios Cruzados , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/antagonistas & inhibidores , 11-beta-Hidroxiesteroide Deshidrogenasa de Tipo 2/sangre , Prueba de Esfuerzo , Frecuencia Cardíaca/fisiologíaRESUMEN
OBJECTIVE: The enzymatic activity of 11ß-hydroxysteroid dehydrogenase-2 (11ß-HSD2) is key to protecting mineral corticoid receptors from cortisol and has been implicated in blood pressure regulation. Grapefruit juice (GFJ) and acidity are thought to inhibit this enzyme in vitro. This study examines the effect of GFJ and intense exercise on 11ß-HSD2 enzyme activity in vivo. SUBJECTS AND METHODS: Eighteen subjects ingested GFJ or apple juice (CON) on separate days prior to reporting to the laboratory in a randomized order. Saliva (Sal) samples were obtained at baseline, 15 and 45 minutes post-treadmill stress test; Sal cortisone (E) and cortisol (F) levels were determined, and the Sal cortisone:cortisol (E:F) ratio was used as an index of 11ß-HSD2 enzyme activity at rest and after intense muscular work. RESULTS: GFJ treatment decreased baseline 11ß-HSD2 enzyme activity (44%) and Sal-E (28%) compared to CON (both, p < 0.05). Sal-E (r = 0.61, p < 0.05) and Sal-F (r = 0.66, p < 0.05) were correlated with diastolic blood pressure (DBP) in GFJ-treated individuals. Treadmill stress significantly increased Sal-E and Sal-F but did not alter 11ß-HSD2 enzyme activity regardless of treatment. When treatments were examined separately, CON 11ß-HSD2 enzyme activity decreased by 36% (p < 0.05) from baseline to 15 post-treadmill exercise. CONCLUSION: Our findings suggest that GFJ and intense muscular work decrease 11ß-HSD-2 activity independently, and no additive effect was noted. The association between DBP and the levels of Sal-F and Sal-E during the GFJ trial should be interpreted cautiously and warrants further investigation.