Myoglobin deficiency impairs maximal oxygen uptake and exercise performance: a lesson from Mb-/- mice.

Myoglobin (Mb) plays an important role at rest and during exercise as a reservoir of oxygen and has been suggested to regulate NO• bioavailability under hypoxic/acidic conditions. However, its ultimate role during exercise is still a subject of debate. We aimed to study the effect of Mb deficiency on maximal oxygen uptake ( V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ ) and exercise performance in myoglobin knockout mice (Mb-/- ) when compared to control mice (Mb+/+ ). Furthermore, we also studied NO• bioavailability, assessed as nitrite (NO2 - ) and nitrate (NO3 - ) in the heart, locomotory muscle and in plasma, at rest and during exercise at exhaustion both in Mb-/- and in Mb+/+ mice. The mice performed maximal running incremental exercise on a treadmill with whole-body gas exchange measurements. The Mb-/- mice had lower body mass, heart and hind limb muscle mass (P < 0.001). Mb-/- mice had significantly reduced maximal running performance (P < 0.001). V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ expressed in ml min-1 in Mb-/ - mice was 37% lower than in Mb+/+ mice (P < 0.001) and 13% lower when expressed in ml min-1  kg body mass-1 (P = 0.001). Additionally, Mb-/- mice had significantly lower plasma, heart and locomotory muscle NO2 - levels at rest. During exercise NO2 - increased significantly in the heart and locomotory muscles of Mb-/- and Mb+/+ mice, whereas no significant changes in NO2 - were found in plasma. Our study showed that, contrary to recent suggestions, Mb deficiency significantly impairs V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ and maximal running performance in mice. KEY POINTS: Myoglobin knockout mice (Mb-/- ) possess lower maximal oxygen uptake ( V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ ) and poorer maximal running performance than control mice (Mb+/+ ). Respiratory exchange ratio values at high running velocities in Mb-/- mice are higher than in control mice suggesting a shift in substrate utilization towards glucose metabolism in Mb-/- mice at the same running velocities. Lack of myoglobin lowers basal systemic and muscle NO• bioavailability, but does not affect exercise-induced NO2 - changes in plasma, heart and locomotory muscles. The present study demonstrates that myoglobin is of vital importance for V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ and maximal running performance as well as explains why previous studies have failed to prove such a role of myoglobin when using the Mb-/- mouse model.

Exercise Training Decreases Nitrite Concentration in the Heart and Locomotory Muscles of Rats Without Changing the Muscle Nitrate Content.

BACKGROUND: Skeletal muscles are postulated to be a potent regulator of systemic nitric oxide homeostasis. In this study, we aimed to evaluate the impact of physical training on the heart and skeletal muscle nitric oxide bioavailability (judged on the basis of intramuscular nitrite and nitrate) in rats. METHODS AND RESULTS: Rats were trained on a treadmill for 8 weeks, performing mainly endurance running sessions with some sprinting runs. Muscle nitrite (NO2-) and nitrate (NO3-) concentrations were measured using a high-performance liquid chromatography-based method, while amino acids, pyruvate, lactate, and reduced and oxidized glutathione were determined using a liquid chromatography coupled with tandem mass spectrometry technique. The content of muscle nitrite reductases (electron transport chain proteins, myoglobin, and xanthine oxidase) was assessed by western immunoblotting. We found that 8 weeks of endurance training decreased basal NO2- in the locomotory muscles and in the heart, without changes in the basal NO3-. In the slow-twitch oxidative soleus muscle, the decrease in NO2- was already present after the first week of training, and the content of nitrite reductases remained unchanged throughout the entire period of training, except for the electron transport chain protein content, which increased no sooner than after 8 weeks of training. CONCLUSIONS: Muscle NO2- level, opposed to NO3-, decreases in the time course of training. This effect is rapid and already visible in the slow-oxidative soleus after the first week of training. The underlying mechanisms of training-induced muscle NO2- decrease may involve an increase in the oxidative stress, as well as metabolite changes related to an increased muscle anaerobic glycolytic activity contributing to (1) direct chemical reduction of NO2- or (2) activation of muscle nitrite reductases.

Health risks for children exercising in an air-polluted environment can be reduced by monitoring air quality with low-cost particle sensors.

A child's body is highly sensitive to air quality, especially regarding the concentration of particulate matter (PM). Nevertheless, due to the high cost of precision instruments, measurements of PM concentrations are rarely carried out in school areas where children spend most of their daily time. This paper presents the results of PM measurements made by a validated, low-cost university air pollution measurement system operating in a rural area near schools. An assessment of children's exposure to PM during school hours (8 a.m.-6 p.m.) at different times of the year was carried out. We show that PM10 concentrations in the air, particularly in winter, often exceeded the alert values of 50 µg m-3, posing a health risk to children, especially when children exercise outside the school building. We also calculated the rate and total PM10 deposition in the respiratory tract during various physical activities performed in clean and polluted air. Monitoring actual PM10 concentrations as presented in this paper, using a low cost sensors, offer school authorities and teachers an opportunity to reduce health risks for children. This can be achieved by adjusting the duration and exercise intensity of children's outdoor physical activities according to the measured air quality.

Training-induced impairment of endothelial function in track and field female athletes.

Professional athletes are often exposed to high training loads that may lead to overfatigue, overreaching and overtraining that might have a detrimental effects on vascular health. We determined the effects of high training stress on endothelial function assessed by the flow-mediated dilation (FMD) and markers of glycocalyx shedding. Vascular examination as well as broad biochemical, hormonal and cardiometabolic evaluation of sprint and middle-distance female runners were performed after 2 months of preparatory training period and compared to age-matched control group of women. Female athletes presented with significantly reduced FMD (p < 0.01) and higher basal serum concentrations of hyaluronan (HA) and syndecan-1 (SDC-1) (p < 0.05 and p < 0.001, respectively), that was accompanied by significantly lower basal serum testosterone (T) and free testosterone (fT) concentrations (p < 0.05) and higher cortisol (C) concentration (p < 0.05). It resulted in significantly lower T/C and fT/C ratios in athletes when compared to controls (p < 0.01). Moreover, fT/C ratio were significantly positively correlated to FMD and negatively to HA concentrations in all studied women. Accordingly, the training load was significantly negatively correlated with T/C, fT/C and FMD and positively with the concentrations of HA and SDC-1. We concluded that young female track and field athletes subjected to physical training developed impairment of endothelial function that was associated with anabolic-catabolic hormone balance disturbances. Given that training-induced impairment of endothelial function may have a detrimental effects on vascular health, endothelial status should be regularly monitored in the time-course of training process to minimalize vascular health-risk in athletes.

Age-related decrease in serum dihydrotestosterone concentration is accompanied by impaired vascular status.

INTRODUCTION: The effect of androgens on the cardiovascular system in humans is ambiguous. Moreover, still little is known about the effects of the most potent androgen, dihydrotestosterone, on arterial stiffness and endothelial function. The aim of this study was to evaluate whether age-dependent alterations in serum concentration of dihydrotestosterone and its circulating metabolite are accompanied by changes in endothelial function and arterial stiffness. METHODS: In 12 young and 11 older men, basal serum concentrations of testosterone, dehydroepiandrosterone sulfate (DHAE-S), androstenedione (AE), dihydrotestosterone (DHT) and androstanediol glucuronide (ADG) were analyzed in relation to vascular status including cIMT - carotid intima media thickness, cAI - central augmentation index, crPWV - carotid radial pulse wave velocity, SI - stiffness index, endothelial and inflammatory markers. RESULTS: Although concentration of testosterone was not different between young and older group, it was demonstrated that DHT, DHEA-S, AE and ADG were significantly lower in older men in comparison to young men (p < 0.01). Interestingly the most surprising difference was found for DHT concentration, that was as much as 61 % lower in aged men that displayed significantly higher values of cIMT, AI, crPWV and SI (p < 10-4), suggestive of arterial stiffness. Furthermore, DHT was negatively correlated to all arterial wall parameters (cAI, crPWV, SI and cIMT), c-reactive protein (CRP) and hyaluronic acid (HA) concentration, as well as positively correlated to markers of endothelial function (MNA and 6-keto-PGF1α) in all studied individuals (n = 23). CONCLUSIONS: We have shown that ageing leads to a significant decrease in DHT concentration that is accompanied by impaired arterial wall characteristics and worsened endothelial function. Therefore more attention should be paid to the DHT, DHEA-S and ADG concentrations as a biomarkers for vascular dysfunction in ageing men.

The impact of aging and physical training on angiogenesis in the musculoskeletal system.

Angiogenesis is the physiological process of capillary growth. It is strictly regulated by the balanced activity of agents that promote the formation of capillaries (pro-angiogenic factors) on the one hand and inhibit their growth on the other hand (anti-angiogenic factors). Capillary rarefaction and insufficient angiogenesis are some of the main causes that limit blood flow during aging, whereas physical training is a potent non-pharmacological method to intensify capillary growth in the musculoskeletal system. The main purpose of this study is to present the current state of knowledge concerning the key signalling molecules implicated in the regulation of skeletal muscle and bone angiogenesis during aging and physical training.

Endurance Training Increases the Running Performance of Untrained Men without Changing the Mitochondrial Volume Density in the Gastrocnemius Muscle.

The activity and quantity of mitochondrial proteins and the mitochondrial volume density (MitoVD) are higher in trained muscles; however, the underlying mechanisms remain unclear. Our goal was to determine if 20 weeks' endurance training simultaneously increases running performance, the amount and activity of mitochondrial proteins, and MitoVD in the gastrocnemius muscle in humans. Eight healthy, untrained young men completed a 20-week moderate-intensity running training program. The training increased the mean speed of a 1500 m run by 14.0% (p = 0.008) and the running speed at 85% of maximal heart rate by 9.6% (p = 0.008). In the gastrocnemius muscle, training significantly increased mitochondrial dynamics markers, i.e., peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) by 23%, mitochondrial transcription factor A (TFAM) by 29%, optic artrophy-1 (OPA1) by 31% and mitochondrial fission factor (MFF) by 44%, and voltage-dependent anion channel 1 (VDAC1) by 30%. Furthermore, training increased the amount and maximal activity of citrate synthase (CS) by 10% and 65%, respectively, and the amount and maximal activity of cytochrome c oxidase (COX) by 57% and 42%, respectively, but had no effect on the total MitoVD in the gastrocnemius muscle. We concluded that not MitoVD per se, but mitochondrial COX activity (reflecting oxidative phosphorylation activity), should be regarded as a biomarker of muscle adaptation to endurance training in beginner runners.

Nitrite Concentration in the Striated Muscles Is Reversely Related to Myoglobin and Mitochondrial Proteins Content in Rats.

Skeletal muscles are an important reservoir of nitric oxide (NO•) stored in the form of nitrite [NO2-] and nitrate [NO3-] (NOx). Nitrite, which can be reduced to NO• under hypoxic and acidotic conditions, is considered a physiologically relevant, direct source of bioactive NO•. The aim of the present study was to determine the basal levels of NOx in striated muscles (including rat heart and locomotory muscles) with varied contents of tissue nitrite reductases, such as myoglobin and mitochondrial electron transport chain proteins (ETC-proteins). Muscle NOx was determined using a high-performance liquid chromatography-based method. Muscle proteins were evaluated using western-immunoblotting. We found that oxidative muscles with a higher content of ETC-proteins and myoglobin (such as the heart and slow-twitch locomotory muscles) have lower [NO2-] compared to fast-twitch muscles with a lower content of those proteins. The muscle type had no observed effect on the [NO3-]. Our results demonstrated that fast-twitch muscles possess greater potential to generate NO• via nitrite reduction than slow-twitch muscles and the heart. This property might be of special importance for fast skeletal muscles during strenuous exercise and/or hypoxia since it might support muscle blood flow via additional NO• provision (acidic/hypoxic vasodilation) and delay muscle fatigue.

Multifactorial Mechanism of Sarcopenia and Sarcopenic Obesity. Role of Physical Exercise, Microbiota and Myokines.

Obesity and ageing place a tremendous strain on the global healthcare system. Age-related sarcopenia is characterized by decreased muscular strength, decreased muscle quantity, quality, and decreased functional performance. Sarcopenic obesity (SO) is a condition that combines sarcopenia and obesity and has a substantial influence on the older adults' health. Because of the complicated pathophysiology, there are disagreements and challenges in identifying and diagnosing SO. Recently, it has become clear that dysbiosis may play a role in the onset and progression of sarcopenia and SO. Skeletal muscle secretes myokines during contraction, which play an important role in controlling muscle growth, function, and metabolic balance. Myokine dysfunction can cause and aggravate obesity, sarcopenia, and SO. The only ways to prevent and slow the progression of sarcopenia, particularly sarcopenic obesity, are physical activity and correct nutritional support. While exercise cannot completely prevent sarcopenia and age-related loss in muscular function, it can certainly delay development and slow down the rate of sarcopenia. The purpose of this review was to discuss potential pathways to muscle deterioration in obese individuals. We also want to present the current understanding of the role of various factors, including microbiota and myokines, in the process of sarcopenia and SO.

Effects of Endurance Training on the Coenzyme Q Redox State in Rat Heart, Liver, and Brain at the Tissue and Mitochondrial Levels: Implications for Reactive Oxygen Species Formation and Respiratory Chain Remodeling.

Sixteen adult, 4-month-old male Wistar rats were randomly assigned to the training group (n = 8) or the control group (n = 8). We elucidated the effects of 8 weeks of endurance training on coenzyme Q (Q) content and the formation of reactive oxygen species (ROS) at the tissue level and in isolated mitochondria of the rat heart, liver and brain. We demonstrated that endurance training enhanced mitochondrial biogenesis in all tested organs, while a significant increase in the Q redox state was observed in the heart and brain, indicating an elevated level of QH2 as an antioxidant. Moreover, endurance training increased the mQH2 antioxidant pool in the mitochondria of the heart and liver, but not in the brain. At the tissue and isolated mitochondria level, an increase in ROS formation was only observed in the heart. ROS formation observed in the mitochondria of individual rat tissues after training may be associated with changes in the activity/amount of individual components of the oxidative phosphorylation system and its molecular organization, as well as with the size of the oxidized pool of mitochondrial Q acting as an electron carrier in the respiratory chain. Our results indicate that tissue-dependent changes induced by endurance training in the cellular and mitochondrial QH2 pool acting as an antioxidant and in the mitochondrial Q pool serving the respiratory chain may serve important roles in energy metabolism, redox homeostasis and the level of oxidative stress.

Lowered Serum Testosterone Concentration Is Associated With Enhanced Inflammation and Worsened Lipid Profile in Men.

The negative relationship between testosterone and inflammatory cytokines has been reported for decades, although the exact mechanisms of their interactions are still not clear. At the same time, little is known about the relation between androgens and acute phase proteins. Therefore, in this investigation, we aimed to study the relationship between androgen status and inflammatory acute phase reactants in a group of men using multi-linear regression analysis. Venous blood samples were taken from 149 men ranging in age from 18 to 77 years. Gonadal androgens [testosterone (T) and free testosterone (fT)], acute phase reactants [C-reactive protein (CRP), ferritin (FER), alpha-1-acid glycoprotein (AAG), and interleukin-6 (IL-6)], cortisol (C), and lipid profile concentrations were determined. It was demonstrated that the markers of T and fT were negatively correlated with all acute phase proteins (CRP, FER, and AAG; p < 0.02) and the blood lipid profile [total cholesterol (TC), low-density lipoprotein (LDL), and triglycerides (TG); p < 0.03]. Multivariate analysis showed that T, fT, and the fT/C ratio were inversely correlated with the CRP, AAG, and FER concentrations independently of age and blood lipids. When adjustment for BMI was made, T, fT, and the fT/C ratio were negatively correlated with the AAG concentrations only. In addition, it was demonstrated that gonadal androgens were positively correlated with physical activity level (p < 0.01). We have concluded that a lowered serum T concentration may promote inflammatory processes independently of adipose tissue and age through a reduced inhibition of inflammatory cytokine synthesis, which leads to enhanced acute phase protein production. Therefore, a low serum T concentration appears to be an independent risk factor in the development of atherosclerosis and cardiovascular diseases. Moreover, the positive correlation between testosterone and physical activity level suggests that exercise training attenuates the age-related decrease in gonadal androgens and, in this way, may reduce the enhancement of systemic low-grade inflammation in aging men.

New Calibration System for Low-Cost Suspended Particulate Matter Sensors with Controlled Air Speed, Temperature and Humidity.

This paper presents a calibration system for low-cost suspended particulate matter (PM) sensors, consisting of reference instruments, enclosed space in a metal pipe (volume 0.145 m3), a duct fan, a controller and automated control software. The described system is capable of generating stable and repeatable concentrations of suspended PM in the air duct. In this paper, as the final result, we presented the process and effects of calibration of two low-cost air pollution stations-university measuring stations (UMS)-developed and used in the scientific project known as Storm&DustNet, implemented at the Jagiellonian University in Kraków (Poland), for the concentration range of PM from a few up to 240 µg·m-3. Finally, we postulate that a device of this type should be available for every system composed of a large number of low-cost PM sensors.

Marathon race performance increases the amount of particulate matter deposited in the respiratory system of runners: an incentive for "clean air marathon runs".

BACKGROUND: In the last decades, marathon running has become a popular form of physical activity among people around the world. It should be noticed that the main marathon races are performed in large cities, where air quality varies considerably. It is well established that breathing polluted air results in a number of harmful effects to the human body. However, there have been no studies to show the impact of marathon run performance on the amount of the deposition of varied fractions of airborne particulate matter (PM) in the respiratory tract of runners. This is why the present study sought to determine the impact of marathon run performance in the air of varying quality on the deposition of the PM1, PM2.5, PM10 in the respiratory tract in humans. METHODS: The PM1, PM2.5 and PM10 deposition was determined in an "average runner" (with marathon performance time 4 h: 30 min) and in an "elite marathon runner" (with marathon performance time 2 h: 00 min) at rest, and during a marathon race, based on own measurements of the PM content in the air and the size-resolved DF(d) profile concept. RESULTS: We have shown that breathing air containing 50 µg m-3 PM10 (a borderline value according to the 2006 WHO standard - still valid) at minute ventilation (VE) equal to 8 L min-1 when at rest, resulted in PM10deposition rate of approximately 9 µg h-1, but a marathon run of an average marathon runner with the VE = 62 L min-1 increased the deposition rate up to 45 µg h-1. In the elite runner, marathon run with the VE= 115 L min-1 increased PM10 deposition rate to 83 µg h-1. Interestingly, breathing the air containing 50 µg m-3of PM10 at the VE = 115 L min-1by the elite marathon runner during the race resulted in the same PM10deposition rate as the breathing highly polluted air containing as much as 466 µg m-3 of PM10 when at rest. Furthermore, the total PM10 deposition in the respiratory tract during a marathon race in average runners is about 22% greater (203 / 166 = 1.22) than in elite runners. According to our calculations, the concentration of PM10in the air during a marathon race that would allow one not to exceed the PM10 deposition rate of 9 µg h-1should be lower than 10 µg m-3 in the case of an average runner, and it should be lower than 5.5 µg m-3 in the case of an elite runner. CONCLUSIONS: We conclude that a marathon run drastically increases the rate of deposition of the airborne PM in the respiratory tract of the runners, as a consequence of the huge VE generated during the race. A decrease of the PM content in the air attenuates this rate. Based on our calculations, we postulate that the PM10 content in the air during a "clean air marathon run", involving elite marathon runners, should be below 5.5 µg m-3.

Physical Activity and Inhibition of ACE Additively Modulate ACE/ACE-2 Balance in Heart Failure in Mice.

Angiotensin-converting enzyme inhibition (ACE-I) and physical activity favorably modulate the ACE/ACE-2 balance. However, it is not clear whether physical activity and ACE-I could synergistically modulate ACE/ACE-2 balance in the course of heart failure (HF). Here, we studied the effects of combined spontaneous physical activity and ACE-I-based treatment on angiotensin (Ang) pattern and cardiac function in a mouse model of HF (Tgαq*44). Tgαq*44 mice with advanced HF (at the age of 12 months) were running spontaneously in a running wheel (exercise training group, ExT) and/or were treated with ACE inhibitor (ACE-I, perindopril, 10 mg/kg) for 2 months. Angiotensin profile was characterized by an LC-MS/MS-based method. The cardiac performance was assessed in vivo by MRI. Ang-(1-7)/Ang II ratio in both plasma and the aorta was significantly higher in the combined treatment group than the ACE-I group or ExT alone, suggesting the additive favorable effects on ACE-2/Ang-(1-7) and ACE/Ang II axes' balance induced by a combination of ACE-I with ExT. The basal cardiac performance did not differ among the experimental groups of Tgαq*44 mice. We demonstrated additive changes in ACE/ACE-2 balance in both plasma and the aorta by spontaneous physical activity and ACE-I treatment in Tgαq*44 mice. However, these changes did not result in an improvement of failing heart function most likely because the disease was at the end-stage. Ang-(1-7)/Ang II balance represents a valuable biochemical end point for monitoring therapeutic intervention outcome in heart failure.

Lung mitochondria adaptation to endurance training in rats.

We elucidated the impact of eight weeks of endurance training on the oxidative metabolism of rat lungs. Adult 3.5-month-old male rats were randomly allocated to a treadmill training group or a sedentary group as control. In the lungs, endurance training raised the expression level of the oxygen sensors hypoxia inducible factor 1α (HIF1α) and lysine-specific demethylase 6A (KDM6A) as well as stimulated mitochondrial oxidative capacity and mitochondrial biogenesis, while lactate dehydrogenase activity was reduced. Endurance training enhanced antioxidant systems (the coenzyme Q content and superoxide dismutase) in lung tissue but decreased them (and uncoupling protein 2) in lung mitochondria. In the lung mitochondria of trained rats, the decreased Q content and Complex I (CI) activity and the enhanced cytochrome pathway activity (CIII + CIV) may account for the diminished Q reduction level, resulting in a general decrease in H2O2 formation by mitochondria. Endurance training enhanced oxidation of glutamate and fatty acids and caused opposite effects in functional mitochondrial properties during malate and succinate oxidation, which were related to reduced activity of CI and increased activity of CII, respectively. In addition, endurance training downregulated CI in supercomplexes and upregulated CIII in the CIII2+CIV supercomplex in the oxidative phosphorylation system. We concluded that the adaptive lung responses observed could be due to hypoxia and oxidative stress induced by strenuous endurance training.

Low-cost air pollution monitoring system-an opportunity for reducing the health risk associated with physical activity in polluted air.

The issue of air pollution by particulate matter (PM) concerns many places in the world. At the same time, many residents undertake physical activity (recreation, rehabilitation, sport) in the open air. Generally, the amount of dust concentration depends on both the place (center or periphery of the city) and the time of day. In the present study we describe the outcome of monitoring of the state of air pollution by particle matter (PM10) in the Kraków agglomeration area in order to show that it can provide information concerning air quality in the area where people practice varied kinds of sports in the open air. The measurements of PM10 have been made by a few stations with identical construction working as one network. The details of the air pollution monitoring system and its data quality verification have been described. The network stations made multipoint observations across the Kraków Metropolitan Area during the year 2017 in eight locations. The locations selected represent a diverse spectrum of terrain conditions in which the Kraków agglomeration community undertakes physical activity. For most months of 2017, the minimum monthly average 4-hour PM10 concentrations were recorded between 10-14 h, regardless of location, whereas the maximum was between 18-22. We also noticed a huge differences in the average monthly value of PM10 in some locations within the Kraków agglomeration-ranging between 4.9-339.0 µg m-3. This indicates that some regions of the city are more suitable for performance of physical activity in the open air than others. In conclusion, we postulate that a low-cost air pollution monitoring system is capable of providing valuable information concerning air quality in a given region, which seems to be of importance also to people who practice varied sports activities in the open air.

Impact of long-lasting spontaneous physical activity on bone morphogenetic protein 4 in the heart and tibia in murine model of heart failure.

Bone morphogenetic protein 4 (BMP4) plays an important role in bone remodeling and in heart failure pathogenesis. The aim of this study was to evaluate the effect of spontaneous physical activity on the expression of BMP4 in the heart and tibia of the transgenic (Tgαq*44) mice, representing a model of chronic heart failure. Tgαq*44 and wild-type FVB mice (WT) were randomly assigned either to sedentary or to trained groups undergoing 8 weeks of spontaneous wheel running. The BMP4 protein expression in heart and tibiae was evaluated using Western immunoblotting and the phosphorus and calcium in the tibiae was assessed using the X-ray microanalysis. BMP4 content in the hearts of the Tgαq*44-sedentary mice was by ~490% higher than in the WT-sedentary mice, whereas in tibiae the BMP4 content of the Tgαq*44-sedentary mice was similar to that in the WT-sedentary animals. Tgαq*44 mice revealed by ~28% poorer spontaneous physical activity than the WT mice. No effect of performed physical activity on the BMP4 content in the hearts of either in the Tgαq*44 or WT mice was observed. However, 8-week spontaneous wheel running resulted in a decrease in the BMP4 expression in tibiae (by ~43%) in the group of Tgαq*44 mice only, with no changes in their bone phosphorus and calcium contents. We have concluded that prolonged period of spontaneous physical exercise does not increase the risk of the progression of the BMP4-mediated pathological cardiac hypertrophy and does not affect bone mineral status in the chronic heart failure mice.

Plasma BCAA concentrations during exercise of varied intensities in young healthy men-the impact of endurance training.

BACKGROUND: Branched-chain amino acids (BCAA) i.e., leucine (Leu), isoleucine (Ile) and valine (Val) are important amino acids, which metabolism play a role in maintaining system energy homeostasis at rest and during exercise. As recently shown lowering of circulating BCAA level improves insulin sensitivity and cardiac metabolic health. However, little is known concerning the impact of a single bout of incremental exercise and physical training on the changes in blood BCAA. The present study aimed to determine the impact of a gradually increasing exercise intensity-up to maximal oxygen uptake (VO2max) on the changes of the plasma BCAA [∑BCAA]pl, before and after 5-weeks of moderate-intensity endurance training (ET). METHODS: Ten healthy young, untrained men performed an incremental cycling exercise test up to exhaustion to reach VO2max, before and after ET. RESULTS: We have found that exercise of low-to-moderate intensity (up to ∼50% of VO2max lasting about 12 min) had no significant effect on the [∑BCAA]pl, however the exercise of higher intensity (above 70% of VO2max lasting about 10 min) resulted in a pronounced decrease (p < 0.05) in [∑BCAA]pl. The lowering of plasma BCAA when performing exercise of higher intensity was preceded by a significant increase in plasma lactate concentration, showing that a significant attenuation of BCAA during incremental exercise coincides with exercise-induced acceleration of glycogen utilization. In addition, endurance training, which significantly increased power generating capabilities at VO2max (p = 0.004) had no significant impact on the changes of [∑BCAA]pl during this incremental exercise. CONCLUSION: We have concluded that an exercise of moderate intensity of relatively short duration generally has no effect on the [∑BCAA]pl in young, healthy men, whereas significant decrease in [∑BCAA]pl occurs when performing exercise in heavy-intensity domain. The impact of exercise intensity on the plasma BCAA concentration seems to be especially important for patients with cardiometabolic risk undertaken cardiac rehabilitation or recreational activity.

Age-Dependent Impairment in Endothelial Function and Arterial Stiffness in Former High Class Male Athletes Is No Different to That in Men With No History of Physical Training.

Background Physical activity is generally considered to exert positive effects on the cardiovascular system in humans. However, surprisingly little is known about the delayed effect of professional physical training performed at a young age on endothelial function and arterial stiffness in aging athletes. The present study aimed to assess the impact of long-lasting professional physical training (endurance and sprint) performed at a young age on the endothelial function and arterial stiffness reported in older age in relation to glycocalyx injury, prostacyclin and nitric oxide production, inflammation, basal blood lipid profile, and glucose homeostasis. Methods and Results This study involved 94 male subjects with varied training backgrounds, including young athletes (mean age ∼25 years), older former high class athletes (mean age ∼60 years), and aged-matched untrained control groups. Aging increased arterial stiffness, as reflected by an enhancement in pulse wave velocity, augmentation index, and stiffness index (P<10-4), as well as decreased endothelial function, as judged by the attenuation of flow-mediated vasodilation (FMD) in the brachial artery (P=0.03). Surprisingly, no effect of the training performed at a young age on endothelial function and arterial stiffness was observed in the former athletes. Moreover, no effect of training performed at a young age (P>0.05) on blood lipid profile, markers of inflammation, and glycocalyx shedding were observed in the former athletes. Conclusions Our study clearly shows that aging, but not physical training history, represents the main contributing factor responsible for decline in endothelial function and increase in arterial stiffness in former athletes.