Increased prevalence of the null allele of the p.Arg577Ter variant in the ACTN3 gene in Brazilian long-distance athletes: A retrospective study.

INTRODUCTION: The phenotypic consequences of the p.Arg577Ter variant in the α-actinin-3 (ACTN3) gene are suggestive of a trade-off between performance traits for speed and endurance sports. Although there is a consistent association of the c.1729C allele (aka R allele) with strength/power traits, there is still a debate on whether the null allele (c.1729T allele; aka X allele) influences endurance performance. The present study aimed to test the association of the ACTN3 p.Arg577Ter variant with long-distance endurance athlete status, using previously published data with the Brazilian population. METHODS: Genotypic data from 203 long-distance athletes and 1724 controls were analysed in a case-control approach. RESULTS: The frequency of the X allele was significantly higher in long-distance athletes than in the control group (51.5% vs. 41.4%; p = 0.000095). The R/X and X/X genotypes were overrepresented in the athlete group. Individuals with the R/X genotype instead of the R/R genotype had a 1.6 increase in the odds of being a long-distance athlete (p = 0.012), whereas individuals with the X/X genotype instead of the R/R genotype had a 2.2 increase in the odds of being a long-distance athlete (p = 0.00017). CONCLUSION: The X allele, mainly the X/X genotype, was associated with long-distance athlete status in Brazilians.

MicroRNAs regulating signaling pathways in cardiac fibrosis: potential role of the exercise training.

Cardiovascular and metabolic diseases such as hypertension, type 2 diabetes, and obesity develop long-term fibrotic processes in the heart, promoting pathological cardiac remodeling, including after myocardial infarction, reparative fibrotic processes also occur. These processes are regulated by many intracellular signaling pathways that have not yet been completely elucidated, including those associated with microRNA (miRNA) expression. miRNAs are small RNA transcripts (18-25 nucleotides in length) that act as posttranscriptionally regulators of gene expression, inhibiting or degrading one or more target messenger RNAs (mRNAs), and proven to be involved in many biological processes such as cell cycle, differentiation, proliferation, migration, and apoptosis, directly affecting the pathophysiology of several diseases, including cardiac fibrosis. Exercise training can modulate the expression of miRNAs and it is known to be beneficial in various cardiovascular diseases, attenuating cardiac fibrosis processes. However, the signaling pathways modulated by the exercise associated with miRNAs in cardiac fibrosis were not fully understood. Thus, this review aims to analyze the expression of miRNAs that modulate signaling pathways in cardiac fibrosis processes that can be regulated by exercise training.

ER stress improvement by aerobic training or enalapril differently ameliorates pathological cardiac remodeling in obese mice.

Overactivation of the classic arm of the renin-angiotensin system (RAS) is one of the main mechanisms involved in obesity-related cardiac remodeling, and a possible relationship between RAS and ER stress in the cardiovascular system have been described. Thus, the aim of this study is to evaluate if activating the protective arm of the RAS by ACE inhibition or aerobic exercise training could overturn diet-induced pathological cardiac hypertrophy by attenuating ER stress. Male C57BL/6 mice were fed a control (SC) or a high-fat diet (HF) for 16 weeks. In the 8th week, HF-fed animals were randomly divided into HF, enalapril treatment (HF-En), and aerobic exercise training (HF-Ex) groups. Body mass (BM), food and energy intake, plasma analyzes, systolic blood pressure (SBP), physical conditioning, and plasma ACE and ACE2 activity were evaluated. Cardiac morphology, and protein expression of hypertrophy, cardiac metabolism, RAS, and ER stress markers were assessed. Data presented as mean ± standard deviation and analyzed by one-way ANOVA with Holm-Sidak post-hoc. HF group had increased BM and SBP, and developed pathological concentric cardiac hypertrophy, with overactivation of the classic arm of the RAS, and higher ER stress. Both interventions reverted the increase in BM, and SBP, and favored the protective arm of the RAS. Enalapril treatment improved pathological cardiac hypertrophy with partial reversal of the concentric pattern, and slightly attenuated cardiac ER stress. In contrast, aerobic exercise training induced physiological eccentric cardiac hypertrophy, and fully diminished ER stress.

Mitigation of Subsequent Ovariectomy Responses through Prior Exercise Training in Rats.

It is well known that cardiometabolic dysfunction gradually increases after menopause and the sedentary lifestyle can aggravated this condition. Therefore, we compared the effects of prior aerobic exercise training in premenopausal period and after ovariectomy (OVX) on metabolic, hemodynamic and autonomic parameters in experimental model of menopause in rats. Female rats were divided in 4 groups: control (C), sedentary OVX (SO), trained OVX (TO), and previously trained OVX (PTO). PTO trained four weeks previously+eight weeks after OVX and the TO group trained only after OVX on a motor treadmill. Autonomic modulation were evaluated and the adipose tissues (WAT) were removed, weighed and lipolysis was assessed. Citrate synthase activity was analysed in the soleus muscle. The trained groups prevented the impairment of BRS in relation to SO; however, only PTO reduced the low frequency band of pulse interval compared to SO. PTO reduced the weight of WAT compared to the other groups; the lipolysis in PTO was similar to C. PTO had preserved muscle metabolic injury in all types of fibres analysed. In conclusion, this study suggests that exercise training should be recommended in a pre-menopausal model in order to prevent cardiometabolic and autonomic menopause-induced deleterious effects.

Circular RNAs as a Diagnostic and Therapeutic Target in Cardiovascular Diseases.

Circular RNAs (circRNAs) are a family of noncoding RNAs (ncRNAs) that are endogenous and widely distributed in different species, performing several functions, mainly their association with microRNAs (miRNAs) and RNA-binding proteins. CVDs remain the leading cause of death worldwide; therefore, the development of new therapies and strategies, such as gene therapies or nonpharmacological therapies, with low cost, such as physical exercise, to alleviate these diseases is of extreme importance for society. With increasing evidence of ncRNA participating in the progression of CVDs, several studies have reported these RNAs as promising targets for diagnosis and treatment. There are several studies of CVDs and the role of miRNAs and lncRNAs; however, little is known about the new class of RNAs, called circRNAs, and CVDs. In this mini review, we focus on the mechanisms of circRNAs and CVDs.

MicroRNAs in type 2 diabetes mellitus: potential role of physical exercise.

Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disease, and its prevalence has grown worldwide. Several pathophysiological processes contribute to the development, progression and aggravating of the disease, for example, decreased insulin synthesis and secretion, insulin resistance, inflammation, and apoptosis, all these processes are regulated by various epigenetic factors, including microRNAs (miRNAs). MiRNAs are small non-coding RNAs, which are around 20 nucleotides in length and are regulators of gene expression at the post-transcriptional level, have a specific function of inhibiting or degrading a messenger RNA target. Thus, miRNAs modulate the expression of many associated genes with the pathophysiological processes in T2DM. On the other hand, miRNAs are also modulated through physical exercise (PE), which induces a change in their expression pattern during and after exercise. Some scientific evidence shows that PE modulates miRNAs beneficially and improves the signaling pathway of insulin resistance, however, little is known about the function of PE modulating miRNAs associated with the processes of insulin secretion, inflammation, and apoptosis. Thus, the objective of this review is to identify the miRNAs expression pattern in T2DM and compare it with the exercise-induced miRNAs expression pattern, identifying the signaling pathways that these miRNAs are regulating in the processes of insulin secretion, insulin resistance, inflammation, and apoptosis in T2DM, and how PE may have a potential role in modulating these signal transduction pathways, promoting benefits for patients with T2DM.

Molecular mechanisms underlying fructose-induced cardiovascular disease: exercise, metabolic pathways and microRNAs.

NEW FINDINGS: What is the central question of this study? What are the mechanisms underlying the cardiac protective effect of aerobic training in the progression of a high fructose-induced cardiometabolic disease in Wistar rats? What is the main finding and its importance? At the onset of cardiovascular disease, aerobic training activates the p-p70S6K, ERK and IRß-PI3K-AKT pathways, without changing the miR-126 and miR-195 levels, thereby providing evidence that aerobic training modulates the insulin signalling pathway. These data contribute to the understanding of the molecular cardiac changes that are associated with physiological left ventricular hypertrophy during the development of a cardiovascular disease. ABSTRACT: During the onset of cardiovascular disease (CVD), disturbances in myocardial vascularization, cell proliferation and protein expression are observed. Aerobic training prevents CVD, but the underlying mechanisms behind left ventricle (LV) hypertrophy are not fully elucidated. The aim of this study was to investigate the mechanisms by which aerobic training protects the heart from LV hypertrophy during the onset of fructose-induced cardiometabolic disease. Male Wistar rats were allocated to four groups (n = 8/group): control sedentary (C), control training (CT), fructose sedentary (F) and fructose training (FT). The C and CT groups received drinking water, and the F and FT groups received d-fructose (10% in water). After 2 weeks, the CT and FT rats were assigned to a treadmill training protocol at moderate intensity for 8 weeks (60 min/day, 4 days/week). After 10 weeks, LV morphological remodelling, cardiomyocyte apoptosis, microRNAs and the insulin signalling pathway were investigated. The F group had systemic cardiometabolic alterations, which were normalised by aerobic training. The LV weight increased in the FT group, myocardium vascularisation decreased in the F group, and the cardiomyocyte area increased in the CT, F and FT groups. Regarding protein expression, total insulin receptor ß-subunit (IRß) decreased in the F group; phospho (p)-IRß and phosphoinositide 3-kinase (PI3K) increased in the FT group; total-AKT and p-AKT increased in all of the groups; p-p70S6 kinase (p70S6K) protein was higher in the CT group; and p-extracellular signal-regulated kinase (ERK) increased in the CT and FT groups. MiR-126, miR-195 and cardiomyocyte apoptosis did not differ among the groups. Aerobic training activates p-p70S6K and p-ERK, and during the onset of a CVD, it can activate the IRß-PI3K-AKT pathway.

Physical exercise effects on the brain during COVID-19 pandemic: links between mental and cardiovascular health.

The current pandemic was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The quarantine period during corona virus disease 19 (COVID-19) outbreak might affect the quality of life leading thousands of individuals to diminish the daily caloric expenditure and mobility, leading to a sedentary behavior and increase the number of health disorders. Exercising is used as a non-pharmacological treatment in many chronic diseases. Here, we review the molecular mechanisms of physical exercise in COVID-19 pandemic on mental health. We also point links between exercise, mental, and cardiovascular health. The infection caused by SARS-CoV-2 affects host cells binding to angiotensin-converting enzyme-2 (ACE2), which is the receptor for SARS-CoV-2. If there is not enough oxygen supply the lungs and other tissues, such as the heart or brain, are affected. SARS-CoV-2 enhances ACE2 leading to inflammation and neuronal death with possible development of mood disorders, such as depression and anxiety. Physical exercise also enhances the ACE2 expression. Conversely, the activation of ACE2/Ang 1-7/Mas axis by physical exercise induces an antiinflammatory and antifibrotic effect. Physical exercise has beneficial effects on mental health enhancing IGF-1, PI3K, BDNF, ERK, and reducing GSK3ß levels. In addition, physical exercise enhances the activity of PGC-1α/ FNDC5/Irisin pathway leading to neuronal survival and the maintenance of a good mental health. Thus, SARS-CoV-2 infection leads to elevation of ACE2 levels through pathological mechanisms that lead to neurological and cardiovascular complications, while the physiological response of ACE2 to physical exercise improves cardiovascular and mental health.

Cardioprotection Generated by Aerobic Exercise Training is Not Related to the Proliferation of Cardiomyocytes and Angiotensin-(1-7) Levels in the Hearts of Rats with Supravalvar Aortic Stenosis.

BACKGROUND/AIMS: The beneficial effect of aerobic exercise training (ET) on cardiac remodeling caused by supravalvar aortic stenosis (AS) has been demonstrated in experimental studies; however, the mechanisms responsible for improving cardiac function are not entirely understood. We evaluated whether ET-generated cardioprotection in pressure-overloaded rats is dependent on cardiomyocyte proliferation, increased angiotensin-(1-7) (Ang-1-7) levels, and its receptor in the myocardium. METHODS: Eighteen weeks after ascending AS surgery, Wistar rats were randomly assigned to four groups: sedentary control (C-Sed), exercised control (C-Ex), sedentary aortic stenosis (AS-Sed) and exercised aortic stenosis (AS-Ex) groups. The moderate treadmill exercise protocol was performed for ten weeks. The functional capacity was assessed by treadmill exercise testing. Cardiac structure and function were evaluated by echocardiogram. Cardiomyocyte proliferation was evaluated by flow cytometry. Expression of cell cycle regulatory genes as CCND2, AURKB, CDK1, and MEIS1 was verified by RT-qPCR. Cardiac and plasma angiotensin I (Ang I), angiotensin II (Ang II), and Ang-(1-7) levels were analyzed by high-performance liquid chromatography (HPLC). The angiotensin-converting enzyme (ACE) activity was assessed by the fluorometric method and protein expression of AT1 and Mas receptors by Western blot. RESULTS: The AS-Ex group showed reduced left ventricular wall relative thickness and improved ejection fraction; also, it showed decreased gene expression of myocyte cell cycle regulators, ACE, Ang I, Ang II and Ang II/Ang-(1-7) ratio levels compared to AS-Sed group. However, ET did not induce alterations in Ang-(1-7) and cardiac Mas receptor expression and myocyte proliferation. CONCLUSION: Aerobic exercise training improves systolic function regardless of myocyte proliferation and Ang-(1-7)/Mas receptor levels. However, the ET negatively modulates the vasoconstrictor/hypertrophic axis (ACE/Ang II) and decreases the expression of negative regulatory genes of the cell cycle in cardiomyocytes of rats with supravalvular aortic stenosis.

Effects of direct high sodium exposure at endothelial cell migration.

The present study aimed to test the hypothesis that high sodium affects the migratory phenotype of endothelial cells (EC) and investigates mechanisms involved independently of hemodynamic factors. Cell migration was evaluated by Wound-Healing at conditions: High Sodium (HS; 160 mM) and Control (CT; 140 mM). O2- production was evaluated by DHE. NADPH oxidase activity was determined by chemiluminescence assay. Expression of adhesion molecules was analyzed by RT-PCR. Shear Stress was performed using a rhythmic shake. Nitric oxide production was measured by Griess reaction. HS-induced impairment in EC migration while both Candesartan and DPI prevented it. HS increased NADPH oxidase activity, which was blocked by Candesartan. Also, HS increased O2- production that was inhibited by Candesartan. HS decreased adhesion molecules expression via ROS (Integrin Alpha 5, Integrin Beta 1, Integrin Beta 3, VE-Cadherin and PECAM) and via AT1R (PECAM). The nitric oxide production induced by shear stress was decreased after EC exposure to HS while both Candesartan and DPI prevented it. Conclusion: This study demonstrated that HS reduced EC migration by AT1R and ROS derived from NADPH Oxidase and mitochondria. The HS reduction in adhesion molecules expression modulated by ROS and AT1R may help to explain the impairment in migration capacity. Also, HS affected EC functionality by reducing their nitric oxide production in response to shear stress.

Exercise training modulates the hepatic renin-angiotensin system in fructose-fed rats.

NEW FINDINGS: What is the central question of this study? What are the effects of exercise training on the hepatic renin-angiotensin system and their contribution to damage resulting from fructose overload in rats? What is the main finding and its importance? Exercise training attenuated the deleterious actions of the angiotensin-converting enzyme/angiotensin II/angiotensin II type 1 receptor axis and increased expression of the counter-regulatory (angiotensin-converting enzyme 2/angiotensin (1-7)/Mas receptor) axis in the liver. Therefore, our study provides evidence that exercise training modulates the hepatic renin-angiotensin system, which contributes to reducing the progression of metabolic dysfunction and non-alcoholic fatty liver disease in fructose-fed rats. The renin-angiotensin system (RAS) has been implicated in the development of metabolic syndrome. We investigated whether the hepatic RAS is modulated by exercise training and whether this modulation improves the deleterious effects of fructose overload in rats. Male Wistar rats were divided into (n = 8 each) control (CT), exercise control (CT-Ex), high-fructose (HFr) and exercise high-fructose (HFr-Ex) groups. Fructose-drinking rats received d-fructose (100 g l-1 ). After 2 weeks, CT-Ex and HFr-Ex rats were assigned to a treadmill training protocol at moderate intensity for 8 weeks (60 min day-1 , 4 days per week). We assessed body mass, glucose and lipid metabolism, hepatic histopathology, angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activity, the angiotensin concentration and the expression profile of proteins affecting the hepatic RAS, gluconeogenesis and inflammation. Neither fructose overload nor exercise training influenced body mass gain and serum ACE and ACE2 activity. The HFr group showed hyperinsulinaemia, but exercise training normalized this parameter. Exercise training was effective in preventing hepatic steatosis and in preventing triacylglycerol and glycogen accumulation. Furthermore, exercise improved the response to the deleterious effects of HFr overload by normalizing the gluconeogenesis pathway and the protein levels of interleukin-6 and tumour necrosis factor-α. The HFr rats displayed increased hepatic ACE activity and protein expression and angiotensin II concentration, which were attenuated by exercise training. Exercise training restored the ACE2/angiotensin-(1-7)/Mas receptor axis. Exercise training may favour the counter-regulatory ACE2/angiotensin-(1-7)/Mas receptor axis over the classical RAS (ACE/angiotensin II/angiotensin II type 1 receptor axis), which could be responsible for the reduction of metabolic dysfunction and the prevention of non-alcoholic fatty liver disease.

Exercise Training and Epigenetic Regulation: Multilevel Modification and Regulation of Gene Expression.

Exercise training elicits acute and adaptive long term changes in human physiology that mediate the improvement of performance and health state. The responses are integrative and orchestrated by several mechanisms, as gene expression. Gene expression is essential to construct the adaptation of the biological system to exercise training, since there are molecular processes mediating oxidative and non-oxidative metabolism, angiogenesis, cardiac and skeletal myofiber hypertrophy, and other processes that leads to a greater physiological status. Epigenetic is the field that studies about gene expression changes heritable by meiosis and mitosis, by changes in chromatin and DNA conformation, but not in DNA sequence, that studies the regulation on gene expression that is independent of genotype. The field approaches mechanisms of DNA and chromatin conformational changes that inhibit or increase gene expression and determine tissue specific pattern. The three major studied epigenetic mechanisms are DNA methylation, Histone modification, and regulation of noncoding RNA-associated genes. This review elucidates these mechanisms, focusing on the relationship between them and their relationship with exercise training, physical performance and the enhancement of health status. On this chapter, we clarified the relationship of epigenetic modulations and their intimal relationship with acute and chronic effect of exercise training, concentrating our effort on skeletal muscle, heart and vascular responses, that are the most responsive systems against to exercise training and play crucial role on physical performance and improvement of health state.

Captopril does not Potentiate Post-Exercise Hypotension: A Randomized Crossover Study.

To evaluate whether captopril (3×50 mg/day) potentiates post-resistance exercise hypotension (PREH) in hypertensives (HT), 12 HT men received captopril and placebo for 4 weeks each in a double-blinded, randomized-crossover design. On each therapy, subjects underwent 2 sessions: Control (C - rest) and Resistance Exercise (RE - 7 exercises, 3 sets to moderate fatigue, 50% of 1 RM -repetition maximum). Measurements were taken before and after 30-60 min (Post1) and 7 h (Post2), and ambulatory blood pressure (BP) was monitored for 24 h. There were no differences in PREH characteristics and mechanisms between the placebo and captopril periods. At Post1, systolic/diastolic BP decreased significantly and similarly after RE with both therapies (Placebo=-13±2/-9±1 mmHg vs. Captopril=-12±2/-10±1 mmHg, P<0.05). RE reduced cardiac output in some subjects and systemic vascular resistance in others. Heart rate and cardiac sympathetic modulation increased, while stroke volume and baroreflex sensitivity decreased after RE (Placebo: +13±2 bpm, +21±5 nu, -11±5 ml, -4±2 ms/mmHg; Captopril: +13±2 bpm, +35±4 nu, 17±5 ml, -3±1 ms/mmHg, P<0.05). At Post2, all variables returned to pre-intervention values. Ambulatory BP was similar between the sessions. Thus, captopril did not potentiate the magnitude and duration of PREH in HT men, and it did not influence PREH mechanisms.

Mesenchymal stem cell therapy associated with endurance exercise training: Effects on the structural and functional remodeling of infarcted rat hearts.

We tested the effects of early mesenchymal stem cell (MSC) therapy associated with endurance exercise on the structural and functional cardiac remodeling of rats with myocardial infarctation (MI). Male Wistar rats (40 days old) were divided into 6 groups: control and exercise sham; control and exercise MI; and control and exercise MI MSC. MI was surgically induced and bone marrow-derived MSCs were immediately injected via caudal vein (concentration: 1 × 10(6 )cells). Twenty-four hours later ET groups exercised on a treadmill (5 days/week; 60 min/day; 60% of maximal running velocity) for 12 weeks. Structural and functional changes were determined by echocardiography. Contractility and intracellular global calcium ([Ca(2 +)]i) transient were measured in myocytes from the left ventricular (LV) non-infarcted area. Calcium regulatory proteins were measured by Western blot. MI increased (p < 0.05) heart, ventricular and LV weights and its ratios to body weight; LV internal dimension in diastole (LVID-D) and in systole (LVID-S) and LV free wall in diastole (LVFW-D), but reduced the thickness of interventricular septum in systole (IVS-S), ejection fraction (EF) and fractional shortening (FS). MI augmented (p < 0.05) the times to peak and to half relaxation of cell shortening as well as the amplitude of the [Ca(2 +)]i transient and the times to peak and to half decay. Early MSCs therapy restored LVFW-D, IVS-S and the amplitude and time to half decay of the [Ca(2 +)]i transient. Early endurance exercise intervention increased (p < 0.05) LVFW-S, IVS-S, EF and FS, and reduced the times to peak and to half relaxation of cell shortening, and the amplitude of the [Ca(2 +)]i transient. Exercise training also increased the expression of left ventricular SERCA2a and PLBser16. Nevertheless, the combination of these therapies did not cause additive effects. In conclusion, combining early MSCs therapy and endurance exercise does not potentiate the benefits of such treatments to structural and functional cardiac remodeling in infarcted rats.

Epigenetic control of exercise training-induced cardiac hypertrophy by miR-208.

Aerobic exercise-induced cardiac hypertrophy (CH) is a physiological response involving accurate orchestration of gene and protein expression of contractile and metabolic components. The microRNAs: miR-208a, miR-208b and miR-499 are each encoded by a myosin gene and thus are also known as 'MyomiRs', regulating several mRNA targets that in turn regulate CH and metabolic pathways. To understand the role of myomiRs in the fine-tuning of cardiac myosin heavy chain (MHC) isoform expression by exercise training-induced physiological hypertrophy, Wistar rats were subjected to two different swim training protocols. We observed that high-volume swim training (T2), improved cardiac diastolic function, induced CH and decreased the expression of miR-208a and miR-208b Consequently, the increased expression of their targets, sex determining region y-related transcription factor 6 (Sox6), Med13, Purß, specificity proteins (Sp)/Krüppel-like transcription factor 3 (SP3) and HP1ß (heterochromatin protein 1ß) was more prominent in T2, thus converging to modulate cardiac metabolic and contractile adaptation by exercise training, with an improvement in the α-MHC/ß-MHC ratio, bypassing the increase in PPARß and histone deacetylase (HDAC) class I and II regulation. Altogether, we conclude that high-volume swim training finely assures physiological cardiac remodelling by epigenetic regulation of myomiRs, because inhibition of miR-208a and miR-208b increases the expression of their target proteins and stimulates the interaction among metabolic, contractile and epigenetic genes.

PBMCs express a transcriptome signature predictor of oxygen uptake responsiveness to endurance exercise training in men.

Peripheral blood cells are an accessible environment in which to visualize exercise-induced alterations in global gene expression patterns. We aimed to identify a peripheral blood mononuclear cell (PBMC) signature represented by alterations in gene expression, in response to a standardized endurance exercise training protocol. In addition, we searched for molecular classifiers of the variability in oxygen uptake (V̇o2). Healthy untrained policemen recruits (n = 13, 25 ± 3 yr) were selected. Peak V̇o2 (measured by cardiopulmonary exercise testing) and total RNA from PBMCs were obtained before and after 18 wk of running endurance training (3 times/wk, 60 min). Total RNA was used for whole genome expression analysis using Affymetrix GeneChip Human Gene 1.0 ST. Data were normalized by the robust multiarray average algorithm. Principal component analysis was used to perform correlations between baseline gene expression and V̇o2peak. A set of 211 transcripts was differentially expressed (ANOVA, P < 0.05 and fold change > 1.3). Functional enrichment analysis revealed that transcripts were mainly related to immune function, cell cycle processes, development, and growth. Baseline expression of 98 and 53 transcripts was associated with the absolute and relative V̇o2peak response, respectively, with a strong correlation (r > 0.75, P < 0.01), and this panel was able to classify the 13 individuals according to their potential to improve oxygen uptake. A subset of 10 transcripts represented these signatures to a similar extent. PBMCs reveal a transcriptional signature responsive to endurance training. Additionally, a baseline transcriptional signature was associated with changes in V̇o2peak. Results might illustrate the possibility of obtaining molecular classifiers of endurance capacity changes through a minimally invasive blood sampling procedure.

Exercise training restores the cardiac microRNA-1 and -214 levels regulating Ca2+ handling after myocardial infarction.

BACKGROUND: Impaired cardiomyocyte contractility and calcium handling are hallmarks of left ventricular contractile dysfunction. Exercise training has been used as a remarkable strategy in the treatment of heart disease. The microRNA-1, which targets sodium/calcium exchanger 1 (NCX), and microRNA-214, which targets sarcoplasmic reticulum calcium ATPase-2a (Serca2a), are involved in cardiac function regulation. Thus, the aim of this study was to evaluate the effect of exercise training on cardiac microRNA-1 and -214 expression after myocardial infarction. METHODS: Wistar rats were randomized into four groups: sedentary sham (S-SHAM), sedentary infarction (S-INF), trained sham (T-SHAM), and trained infarction (T-INF). Exercise training consisted of 60 min/days, 5 days/week for 10 weeks with 3 % of body weight as overload beginning four weeks after myocardial infarction. RESULTS: MicroRNA-1 and -214 expressions were, respectively, decreased (52 %) and increased (54 %) in the S-INF compared to the S-SHAM, while exercise training normalized the expression of these microRNAs. The microRNA targets NCX and Serca-2a protein expression were, respectively, decreased (55 %) and increased (34 %) in the T-INF group compared to the S-INF group. CONCLUSIONS: These results suggest that exercise training restores microRNA-1 and -214 expression levels and prevents change in both NCX and Serca-2a protein and gene expressions. Altogether, our data suggest a molecular mechanism to restore ventricular function after exercise training in myocardial infarction rats.

Resistance training regulates cardiac function through modulation of miRNA-214.

AIMS: To determine the effects of resistance training (RT) on the expression of microRNA (miRNA)-214 and its target in sarcoplasmic reticulum Ca2+-ATPase (SERCA2a), and on the morphological and mechanical properties of isolated left ventricular myocytes. MAIN METHODS: Male Wistar rats were divided into two groups (n = 7/group): Control (CO) or trained (TR). The exercise-training protocol consisted of: 4 × 12 bouts, 5×/week during 8 weeks, with 80% of one repetition maximum. KEY FINDINGS: RT increased the left ventricular myocyte width by 15% and volume by 12%, compared with control animals (p < 0.05). The time to half relaxation and time to peak were 8.4% and 4.4% lower, respectively, in cells from TR group as compared to CO group (p < 0.05). RT decreased miRNA-214 level by 18.5% while its target SERCA2a expression were 18.5% higher (p < 0.05). SIGNIFICANCE: Our findings showed that RT increases single left ventricular myocyte dimensions and also leads to faster cell contraction and relaxation. These mechanical adaptations may be related to the augmented expression of SERCA2a which, in turn, may be associated with the epigenetic modification of decreased miRNA-214 expression.

Phytochemistry Profile, Antimicrobial and Antitumor Potential of the Methanolic Extract of Tabernaemontana catharinensis A DC and Eragrostis plana NEES.

Natural compounds that have the potential to act as antimicrobials and antitumors are a constant search in the field of pharmacotherapy. Eragrostis plana NEES (Poaceae) is a grass with high allelopathic potential. Allelopathy is associated with compounds generated in the primary and secondary metabolism of the plant, which act to protect it from phytopathogens. Tabernaemontana catharinensis A DC (Apocynaceae), a tree in which its leaves and bark are used for the preparation of extracts and infusions that have anti-inflammatory and antinociceptive effects, is attributed to its phytochemical constitution. The objective of this study was to elucidate the phytochemical constitution, the antibacterial potential, the toxicity against immune system cells, hemolytic potential, and antitumor effect of methanolic extracts of E. plana and T. catharinensis. The phytochemical investigation was carried out using the UHPLC-QTOF MS equipment. The antibacterial activity was tested using the broth microdilution plate assay, against Gram-negative and Gram-positive strains, and cytotoxicity assays were performed on human peripheral blood mononuclear cells (PBMC) and in vitro hemolysis. Antitumor activity was performed against the colon cancer cell line (CT26). Results were expressed as mean and standard deviation and analyzed by ANOVA. p < 0.05 was considered significant. More than 19 possible phytochemical constituents were identified for each plant, with emphasis on phenolic compounds (acids: vanillic, caffeic, and quinic) and alkaloids (alstovenine, rhyncophylline, amezepine, voacangine, and coronaridine). Both extracts showed antibacterial activity at concentrations below 500 µg/mL and were able to decrease the viability of CT26 at concentrations below 2000 µg/mL, without showing cytotoxic effect on PBMCs and in vitro hemolysis at the highest concentration tested. This is the first report of the activity of E. plana and T. catharinensis extracts against colon cancer cell line (CT26). Studies should be carried out to verify possible molecular targets involved in the antitumor effect in vivo.

Resistance Training Reduces Blood Pressure: Putative Molecular Mechanisms.

Arterial hypertension is a multifactorial clinical condition characterized by higher blood pressure levels. The main treatment for controlling high blood pressure consists of drug therapy, but the scientific literature has been pointing to the efficiency of aerobic and resistance exercises acting in a therapeutic and/or preventive way to reduce and control the blood pressure levels. Resistance training is characterized by sets and repetitions on a given muscle segment that uses overload, such as machine weights, bars, and dumbbells. As it successfully affects a number of variables associated to practitioners' functional and physiological features as well as emotional and social variables, resistance training has been a crucial part of physical exercise programs. Several reports highlight the various adaptive responses it provides, with a focus on the improvement in strength, balance, and muscular endurance that enables a more active and healthy lifestyle. Resistance training programs that are acute, sub-chronic, or chronic can help people with varying ages, conditions, and pathologies reduce their arterial hypertension. However, molecular mechanisms associated with resistance training to reduce blood pressure still need to be better understood. Thus, we aimed to understand the main effects of resistance training on blood pressure as well as the associated molecular mechanisms.