bluuebunny/crossref_metadata_2025_split huggingface dataset:
The renin angiotensin system (RAS) in the heart: Effects of aerobic training
Authors: Silva Sebastiao Donato , Jara Zaira Palomino , Moreira Roseli , Montezano Augusto , Casarini Dulce , Touyz Rhian , Michelini Lisete Compagno 
Published: November 2023

GoalsTo investigating the sequential effects of aerobic training on cardiac Ang II/Ang (1–7) ratio and its relationship with cardiac hypertrophy and inflammatory markers.MethodsMale SHR were trained (T) or kept sedentary (S) for 2 months. After measurement of resting arterial pressure (AP) and heart rate (HR) at weeks 0 (S0), 1 (T1), 2 (T2), 4 (T4) e 8 (S8 and T8) rats were euthanized for heart harvesting. Ang II and Ang (1–7) (HPLC), oxidative stress (DHE staining) and genic expression of hypertrophy and inflammatory markers were measured in the left ventricle (LV). WKY rats were used as time‐controlResultsSHR‐S0 vs. WKY‐S0 had higher AP and HR (169±1 mmHg; 358±7 bpm), LV hypertrophy (corresponding to increases of +27% in LV/BW and 2.4‐, 3.9‐ and 4.0‐fold in α‐MHC, β‐MHC and α‐actin, respectively), increased ROS density (+19%) and elevated TNFα expression (2.8‐fold) in LV, but similar Ang II and Ang‐(1–7) content (87±3 and 54±3 pmol/g tissue, respectively). In the SHR, T promptly reduced LV Ang II (−71%, T1), increased Ang‐(1–7) (+30%, T2) and reduced and normalized DHE density (T2), with a transitory increase of IL‐1b and TNFα (T1‐T2) and a transitory decrease of β‐MHC (T1) and α‐MHC (T2). LV Ang II/Ang (1–7) ratio reduction (−73%) and normalization of ROS content were maintained up to T8, while β‐MHC (T8), IL‐1b and TNFα (T4‐T8) were reduced below S levels. In the SHR‐T, α‐MHC and α‐actin were still higher and LV/BW similar to that of SHR‐S at the end of protocols. T effects were accompanied by HR (−15%, T4‐T8) and AP (−10%, T8) reductions.ConclusionAlthough not reducing LV hypertrophy of the SHR, training reduces RAS vasoconstrictor, proliferative and trophic axis, improves oxidative stress (early normalization) and reduces the pro‐inflammatory profile and β‐MHC expression (late effects) in the heart.Support or Funding InformationFapesp; Capes; Cnpq
Resveratrol Consumption and RIP140 Knockout Mice Demonstrate a Novel Relationship between Increased Mitochondrial Content and Compromised Bone Mineral Mass, Microarchitecture, and Strength
Authors: Miotto Paula M , Frendo‐Cumbo Scott , Sacco Sandra M , Wright David C , Ward Wendy E , Holloway Graham P 
Published: November 2023

The polyphenol resveratrol (RSV) is associated with many health benefits, including the prevention of high fat (HF) diet induced glucose‐intolerance. However, the off‐target effects of resveratrol on bone health, specifically within the context of diet induced glucose‐intolerance, is unknown. The purpose of this study was to evaluate, in tibias, the effect of RSV on bone microarchitecture, mineral mass, and strength. Moreover, we aimed to elucidate molecular adaptations within bone that could provide insight regarding the impact of RSV on bone health. Male C57BL6 mice (8 weeks old) were randomized to 1 of 3 diets: control, CON (10% fat), HF (60% fat), or HF‐RSV (100mg/kg/day) for 12 weeks. Glucose‐tolerance tests verified that the HF diet induced glucose‐intolerance and that RSV prevented this effect. Combined HF‐RSV consumption led to compromised trabecular microarchitecture, lower bone mineral mass, and lower bone strength. This corresponded with elevated markers of osteoclast activation (decreased ratio of osteoprotegerin to receptor activator of nuclear factor kappa‐B ligand), bone resorption (cathepsin K), and increased mitochondrial content (electron transport chain complex subunits I–V). Further, we demonstrated proof‐of‐principle that elevated bone mitochondrial content is inversely related to bone health. Specifically, we utilized RIP140 knockout (KO) mice, a molecular model of elevated mitochondrial content. Similar to HF‐RSV mice, RIP140 KO mice displayed elevated mitochondrial content and compromised bone microarchitecture, bone mineral, and bone strength. This corresponded with higher markers of osteoclast activation and bone resorption, similar to HF‐RSV mice. Together, these findings suggest that although RSV successfully mitigates HF diet induced glucose‐intolerance, there can be negative consequences on bone health. Further, insulin sensitizing agents that are known to increase mitochondrial biogenesis should be considered for off‐target effects on bone health, as these data demonstrate that elevations in bone mitochondrial content are associated with decrements in bone health.Support or Funding InformationSupported by NSERC, OMAFRA, and CFI, Canada.
Treadmill exercise with robotic resistance improves stepping and enhances synaptic plasticity in spinal cord injured rats
Authors: Ruiz Emanuel , Villanueva Silvia , Estrada Christina , Hinahon Erika , Traughber Terence , Sirot Steve , Robles Madely , Martinez Richard , de Leon Ray 
Published: November 2023

It has been shown that robotic‐assisted treadmill training with body weight support improves the recovery of stepping patterns after a spinal cord injury (SCI). We examined the effects of robotic‐applied resistive forces in a rodent model of SCI. Thirty‐three female Sprague Dawley rats received a severe mid‐thoracic spinal cord contusion injury. A baseline test was performed two weeks later, after which treadmill training using a robotic device to apply viscous forces that opposed horizontal or vertical movements of the hind limbs. One group rats (n=10) was trained with a robotic horizontal force (HF) and another group (n=7) was trained with a vertical force (VF), another group Trained (T) without force (n=8) and one group was untrained (UT) (n=8). Training was performed for 15 minutes/day, 5 days/week. After 6 weeks of training with robotic resistive forces, improvements in step cycle kinematics were observed based on data collected by the robotic device. Specifically, training with the HF significantly increased step length and forward displacement by 24% and 16% respectively relative to untrained controls. Training with VF did not affect step length parameters but instead impacted vertical velocity. Specifically, training with VF significantly increased peak vertical velocity during lift and peak vertical velocity prior to paw contact by 49% and 40% respectively. These findings suggested that treadmill training with HF and VF was effective in shaping hind limb movements in SCI rats. We next performed immunohistochemical analyses of biochemical markers for synaptic plasticity in the ventral horn of the lumbar spinal cord. The expression of synaptophysin was significantly greater after HF training compared to VF and T training (p<0.05). This finding suggested that HF training increased synapses in the lumbar spinal cord more so than other forms of training. Interestingly, a high level of synaptophysin expression was also observed in UT rats and was similar to the expression associated with HF training. On‐going experiments with VGLUT and GLYT2 labeling around motor neurons will provide greater insight into the nature of these synapses. These findings have implications for the use of treadmill exercise therapies following SCI.Support or Funding InformationNIH grant R15NS082711 to R. de Leon
Effects in young men of isometric handgrip training (IHG) on endothelium‐dependent vasodilator responses in the contralateral arm: changes in the contribution of cyclooxygenase (COX) products
Authors: Tsitoglou Kyriakos , Martin Una , Marshall Janice 
Published: November 2023

Previous studies have shown that IHG and rhythmic handgrip training can reduce arterial blood pressure (ABP), especially in hypertensive subjects. The mechanisms underlying these effects are unclear, but it has been proposed that IHG training achieves its effects mainly by decreasing sympathetic activity. However, in hypertensive patients, IHG decreases plasma markers of oxidative stress. Thus, we tested the hypothesis in young normotensive men, that IHG improves endothelial function remotely, in the non‐trained arm. In 10 recreationally‐active men (18–25 years), we used laser Doppler fluximetry on the non‐dominant forearm to record changes in cutaneous red cell flux (RCF) evoked by iontophoresis of acetylcholine (ACh, 8 × 20s pulses: 7 at 100 μA, 8th at 200 μA, at 60s intervals), and following release of arterial occlusion for 3 min (reactive hyperaemia) before and after IHG training of the dominant forearm. IHG training comprised 4×3 min contractions at 30% Maximum voluntary contraction (MVC) at 5 min intervals, 4 days/week for 4 weeks. Before and after IHG training, we tested the contribution of COX products to dilator responses. IHG training did not affect resting ABP: 124±1.8/70±1.7 vs 125±1.8/72±1.6 mmHg. As expected, MVC was increased in the trained arm (29.0±1.3 vs 33.5±1.5Kg: P<0.05, paired t‐test), but not in the contralateral arm (26±0.9 vs 27.1±2.6Kg). Before training, ACh‐induced dilator responses were unaltered by COX inhibition with aspirin (600mg p.o.): maximum RCF 192.2±5.5 vs 182.6±4.7 PU respectively), suggesting any contribution of COX dilator and constrictor products was balanced. By contrast, aspirin attenuated peak reactive hyperaemia from 92.9±2.5 to 75.07± 2.58PU (P<0.05 : RMANOVA) indicating a contribution of COX dilator products. After IHG training, neither the magnitude of ACh‐induced dilatation, nor reactive hyperaemia was changed, but aspirin now augmented the ACh response: maximum RCF 192.6±4.1 increased to 227.5±5.2PU (P<0.001), but had no effect on reactive hyperaemia (92.1±2.3 vs 91.8±3.6PU). These results suggest that in young normotensive men, IHG training of one arm has no effect on ABP and no net effect on the magnitude of endothelial‐dependent dilatation remotely, but does change the balance of influence of vasoconstrictor and dilator COX products. We propose that during IHG training, the contribution of COX dilator products to endothelium‐dependent, agonist‐evoked dilatation and reactive hyperaemia is attenuated and replaced with the influence of another dilator such as nitric oxide, leaving vasoconstrictor COX products limiting even greater agonist‐induced dilatation.Support or Funding InformationAlexander S. Onassis Public Benefit Foundation
Effects of isometric handgrip (IHG) training of one forearm on reactive and exercise hyperaemia in the ipsilateral and contralateral arm of White European Young Men
Authors: Tsitoglou Kyriakos , Martin Una , Marshall Janice 
Published: November 2023

There is evidence that IHG training reduces arterial blood pressure (ABP), particularly in hypertensive subjects and that it may also enhance reactive hyperaemia in the trained arm. We have tested in normotensive, young men, whether IHG improves reactive and exercise hyperaemia in the contralateral, untrained arm, which would be evidence of remote effects on dilator function. The study was performed on 10 recreationally active, White European men (18–25 years). IHG training comprised 4×3 min contractions at 30% Maximum voluntary contraction (MVC) at 5 min intervals, 4 days/week for 4 weeks, undertaken with the dominant arm. Before and after IHG training, forearm blood flow (FBF) was recorded by venous occlusion plethysmography in the trained arm and non‐trained contralateral arm, at rest and at intervals after 3‐mins arterial occlusion (reactive hyperemia), or 3‐min rhythmic handgrip contractions at 60% Maximum voluntary contraction (MVC; exercise hyperemia). As expected, MVC was increased after IHG training in the trained arm (29.0±1.3, vs 33.5±1.5*Kg, *: P< 0.01, paired t‐test), but not in the untrained arm (27.0±0.9 vs 27.1±0.9Kg). IHG training did not affect resting ABP: 124±1.8/70±1.7 vs 125±1.8/72±1.6 mmHg, or resting FBF: 4–9±0.9 vs 5.1±0.8 ml.min−1.100ml−1 in dominant arm before vs after IHG training. However, reactive hyperaemia was increased in both the trained arm and non‐trained arm by IHG training: peak FBF increased from 41.4±1.9 to 50.8±2.0* ml.min−1. 100ml−1 (*: P< 0.01 RMANOVA) in the trained arm, and from 41.3±4.8 to 52.8 ± 1.7* ml.min−1. 100ml−1 in the non‐trained arm. Further, exercise hyperaemia was increased in both arms by IHG training, peak FBF was increased from 75.6±2.5 to 110.2±2.6* ml.min−1. 100ml−1 in the trained arm and from 77.8±9.4 to 101.1±2.9* ml.min−1. 100ml−1. These results indicate that in healthy young men, IHG training of one arm for 4 weeks improves peak muscle power and induces a parallel increase in exercise hyperaemia associated with submaximal isometric contraction in the trained arm. In addition, our results indicate for the first time, that not only is there a concomitant increase in reactive hyperaemia in the trained arm, but also a substantial increase in reactive hyperaemia and in exercise hyperaemia to submaximal contraction in the contralateral, non‐trained arm, in the absence of a change in muscle power. The mechanisms underlying these changes remain to be determined but we propose that they reflect a generalised beneficial effect of IHG training on endothelial dilator function.Support or Funding InformationAlexander S. Onassis Public Benefit Foundation
An Eight‐Week Exercise Program Increased Exhaled Nitric Oxide (FENO) Levels in Adolescents
Authors: Shin Hye‐Won , Cooper Dan , Haddad Fadia , Lu Kim , Aizik Shlomit 
Published: November 2023

RATIONALEExhaled NO (FENO) measurement is a non‐invasive tool to assess airways inflammation. However, little is known about how exercise training affects nitric oxide (NO) levels in human airways. We hypothesized that aerobic training program will increase FENO due to inflammation from repeated bouts of exercise.METHODS17 healthy and 5 asthmatic (4 are on ICS) adolescents (14–17 y/o) completed an eight‐week exercise program (1 hour/session, 3 days/week). FENO and lung functions were collected before and after ten two‐min bouts of cycle ergometer exercise (~72% peak VO2 max) prior and at the end of the training program. FENO50 was obtained according to the ATS guideline using a chemiluminescence analyzer (NIOX, Aerocrine AB, Sweden). FENO were also measured utilizing multiple constant flow rate maneuvers at 100, 150, and 200 ml/s to estimate maximum airway wall flux (JawNO) and alveoli NO (CANO). Lung function was assessed using spirometry. Blood IgE levels were obtained prior and at the end of the training program.RESULTSMean (SD) FENO50 levels at baseline were 17 (6) for controls and 17 (7) for asthmatics. Following training we observed substantial variability in FENO levels in both healthy and asthmatic adolescents (Figure 1). The JawNO was increased for those who with increased FENO50 following exercise training (658 (358) pl/s at pre‐training vs. 1149 (884) pl/s at post‐training). CANO did not changed following training (2.7 (2.7) ppb at pre‐training vs. 4.5 (5.1) ppb at post‐training). After a brief exercise, the mean (SD) change of FENO50 regardless of training status was −11.1 (23.9) in healthy controls and −12 (15.8) in asthmatics. In contrast to FENO, the lung function indices (i.e., FEV1/FVC, FEF25‐75) were not changed following exercise challenge nor following exercise training. In addition, there is no relationship between blood IgE levels and the changes in FENO levels following exercise training.CONCLUSIONSThis study demonstrates that exercise training generates substantial changes in FENO levels in certain individuals. This result may suggest, in part, that increased levels of inflammatory mediators with repeated bouts of exercise following training may stimulate NO production in the human airways.Support or Funding InformationThis work was supported by NIH Program Project Grant P01 HD048721.
Influence of High Intensity Power Training on Central Arterial Stiffness in Young Healthy Subjects
Authors: Ellis Brian , Wells Andrew , Smith Michael 
Published: November 2023

PURPOSEIt is currently understood that aerobic exercise training can decrease central arterial stiffness, whereas resistance training may increase central arterial stiffness. Recently, high intensity power training (HIPT) has grown in popularity, and the effect of this novel training on central arterial stiffness remains unknown. Therefore, our goal was to investigate the effect of HIPT on central pulse wave velocity (cPWV) in healthy young men and women.METHODSubjects were randomized to a control group (N=2) or training group (N=5). The training group participated in HIPT training three times a week for 8 weeks. Each session consisted of a combination of multi‐joint exercises such as the squat, deadlift, and bench press, along with olympic movements such as the clean, jerk, and snatch, as well as other functional exercises that were completed for time, or as many repetitions as possible (AMRAP). PWV was measured using applanation tonometry at the carotid and femoral arteries at the outset of the training, and again eight weeks later. A 30‐second recording of each site was simultaneously obtained for later analysis. The foot of each arterial pulse wave was marked, a time difference was calculated, and finally averaged into a mean time value. The cPWV was calculated using eighty percent of the distance between measurement sites divided by the mean time value.RESULTSIn the control group, cPWV did not change from pre‐ to post‐training (8.0 m/s vs. 7.9 m/s; P=0.94), whereas cPWV increased in the training group, but was not statistically significant (8.2 m/s vs. 9.2 m/s; P=0.08).CONCLUSIONSOur results suggest that there may be unfavorable cardiovascular adaptations associated with participation in HIPT absent a traditional aerobic training component. Further research using a more robust sample size is indicated to find a significant conclusion.
Aerobic Interval Training Improves Hemodynamic Response to Exercise by Enhancing Production and Function of Monocyte‐derived Endothelial Progenitor Cells
Authors: Wang Jong‐Shyan 
Published: November 2023

Monocyte‐derived endothelial progenitor cells (monocyte‐derived EPCs) potentially incorporate into the injured vessels and subsequently trans differentiate into vascular endothelial cells. This study explicates the manner in which interval and continuous exercise regimens affect central/peripheral hemodynamic responses to exercise by modulating various monocyte‐derived EPC subsets. Sixty healthy sedentary males were randomized to engage either aerobic exercise training (AIT, 3‐minute intervals at 40% and 80% VO2max, n=20) or moderate continuous training (MCT, sustained 60% VO2max, n=20) for 30 minutes/day, 5 days/week for 6 weeks, or to a control group that did not received exercise intervention (n=20). Monocyte‐derived EPC characteristics and angiogenic factor production were measured at rest and following hypoxic exercise test (HE, 100W under 12%O2). The results demonstrated that AIT exhibited larger improvements in VO2max, peak cardiac output (QH) and peak perfusions of frontal cerebral lobe (QFC) and vastus lateralis (QVL), and flow‐mediated vasodilation (FMD) of brachial artery than the MCT group. Furthermore, AIT (i) increased circulating Mono‐1 and Mono‐2 EPC counts; (ii) diminished the shedding of endothelial cells; and (iii) promoted the migration and tube formation of EPCs at rest or following HE, compared to those of MCT. Additionally, Mono‐1 and ‐2 EPC counts were directly related to VO2max, peak QH/QFC/QVL levels, and FDM. Therefore, we conclude that AIT is superior to MCT for enhancing aerobic capacity and hemodynamic responses to exercise, possibly by promoting the mobilization/functionality of monocyte‐derived EPCs.Support or Funding InformationNational Science Council of Taiwan (grant number NSC 100‐2314‐B‐182‐004‐MY3), Chang Gung Medical Research Program (grant number CMRPD3D0131), and Healthy Aging Research Center, Chang Gung University (grant number EMRPD1A0841)
Endurance Training Alters Expression of Over 3000 Isoforms and 34 Novel Transcripts in Human Skeletal Muscle
Authors: Lindholm Malene , Giacomello Stefania , Solnestam Beata Werne , Fischer Helene , Kjellqvist Sanela , Huss Mikael , Sundberg Carl Johan 
Published: November 2023

Background and objectiveLong‐term endurance training has many beneficial effects on both skeletal muscle function and health and prevents many common diseases e.g., cardiovascular disease, type II diabetes and obesity. The mechanisms of molecular adaptation regulating these effects are not fully understood. To date, global transcriptome changes in skeletal muscles have been studied at gene level. However, global isoform expression changes following exercise training in humans are hitherto unknown. The objective of the present study was thus to investigate endurance‐induced global isoform expression changes, as well as potential transcriptional effects on previously unannotated parts of the genome with training.Methods and results23 healthy volunteers trained only one leg for a three‐month period (45 min, 4 times per week). Before and after the training period, skeletal muscle biopsies were obtained from m. vastus lateralis of both legs. One‐legged performance and citrate synthase activity significantly increased with training and there were significant differences between the trained and untrained legs. Global isoform expression analysis (from 2×100 base pairs paired‐end RNA sequencing) of all biopsies showed a highly training‐specific response. Using multivariate statistics, we found 3404 differentially expressed isoforms, mainly associated with energy production through oxidative phosphorylation. Several genes had many isoforms that changed significantly, for example 5 isoforms of CAPN3 (a protease), 4 different isoforms of MDH1 (citric acid cycle), 8 isoforms of NEB (within sarcomeres) and 6 isoforms of PDHA1 (pyruvate dehydrogenase complex). 54 genes had isoforms that were differentially expressed in opposite directions. In addition, 34 novel transcripts, several showing protein‐coding potential, significantly changed with training.ConclusionThis human training study induced consistent differential expression of isoforms and novel transcripts that were concordant with the phenotypic adaptation. It is likely that the observed differential isoform expression to a large degree reflect adaptation mechanisms and processes that contribute to the functional and health benefits that are known to follow regular physical activity.Support or Funding InformationThis work was supported by the Swedish National Centre for Research in Sports, Karolinska Institutet PhD funding (KID) and the Wallenberg Advanced Bioinformatics Infrastructure