Classically, the relationship between systolic BP (SBP) and clinical outcome was described as U-or J shaped, with both high and low values of BP being independent prognostic factors for poor outcome.2,3 Nonetheless, these studies did not consider the recanalization state of the affected arterial territory, which may directly influence the hemodynamic response.The main objective of this study is to determine the relationship between BP during the first 24 hours after ischemic stroke and clinical outcome in patients submitted to intravenous or intra-arterial recanalization treatments. Methods Study PopulationWe included consecutive patients with acute ischemic stroke from July 2009 to June 2015, treated with intravenous thrombolysis (IVrtPA) or intra-arterial therapies in our tertiary, university hospital in Portugal. The exclusion criteria were as follows: patients who had insufficient BP data (ie, incomplete BP readings in the first 24 hours poststroke due to patient death or early hospital transfer); unavailable information Background and Purpose-Historical stroke cohorts reported a U-or J-shaped relationship between blood pressure (BP) and clinical outcome. However, these studies predated current revascularization strategies, disregarding the recanalization state of the affected arterial territory. We aimed to investigate the relationship between BP in the first 24 hours after ischemic stroke and clinical outcome in patients submitted to intravenous or intra-arterial recanalization treatments. Methods-Consecutive patients with acute stroke treated with intravenous thrombolysis or intra-arterial therapies were enrolled in a retrospective cohort study. BP was measured on regular intervals throughout day and night during the first 24 hours after stroke onset. The mean systolic BP and diastolic BP during the first 24 hours post stroke were calculated.Recanalization was assessed at 6 hours by transcranial color-coded Doppler, angiography, or angio-computed tomography.Functional outcome was assessed at 3 months by modified Rankin Scale. Linear and quadratic multivariate regression models were performed to determine associations between BP and functional outcome for the whole population and recanalyzed and nonrecanalyzed patients. Results-We Conclusions-Systemic

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Background. We investigated the effects of exercise training (ET) on miR-126 levels and skeletal muscle angiogenesis in obese Zucker rats. Results. Zucker rats were randomly assigned to sedentary and swimming-trained groups: lean sedentary (LS) and trained (LTR); obese sedentary (OB) and trained (OBTR). The OB group displayed capillary rarefaction compared with the LS group. In contrast, ET increased the capillary/fiber ratio by 38% in the LTR group and normalized capillary rarefaction in the OBTR group. VEGF, PI3K, and eNOS levels were reduced in the skeletal muscle of the OB group. ET normalized VEGF, PI3K, and eNOS levels in OBTR, contributing to vascular network homeostasis. PI3KR2 inhibits PI3K, a key mediator of the VEGF signaling pathway. Obesity decreased miR-126 and increased PI3KR2 levels compared with the LS group. However, ET normalized miR-126 levels in the OBTR group versus the LS group and decreased expression of PI3KR2. Conclusion. Our findings show that obesity leads to skeletal muscle capillary rarefaction, which is regulated by decreased miR-126 levels and increased PI3KR2. Inversely, ET normalizes miR-126 levels and VEGF signaling and should be considered an important therapeutic strategy for vascular disorders.

Background The exercise intolerance in chronic heart failure with reduced ejection fraction (HFrEF) is mostly attributed to alterations in skeletal muscle. However, the mechanisms underlying the skeletal myopathy in patients with HFrEF are not completely understood. We hypothesized that (i) aerobic exercise training (AET) and inspiratory muscle training (IMT) would change skeletal muscle microRNA‐1 expression and downstream‐associated pathways in patients with HFrEF and (ii) AET and IMT would increase leg blood flow (LBF), functional capacity, and quality of life in these patients. Methods Patients age 35 to 70 years, left ventricular ejection fraction (LVEF) ≤40%, New York Heart Association functional classes II–III, were randomized into control, IMT, and AET groups. Skeletal muscle changes were examined by vastus lateralis biopsy. LBF was measured by venous occlusion plethysmography, functional capacity by cardiopulmonary exercise test, and quality of life by Minnesota Living with Heart Failure Questionnaire. All patients were evaluated at baseline and after 4 months. Results Thirty‐three patients finished the study protocol: control (n = 10; LVEF = 25 ± 1%; six males), IMT (n = 11; LVEF = 31 ± 2%; three males), and AET (n = 12; LVEF = 26 ± 2%; seven males). AET, but not IMT, increased the expression of microRNA‐1 (P = 0.02; percent changes = 53 ± 17%), decreased the expression of PTEN (P = 0.003; percent changes = −15 ± 0.03%), and tended to increase the p‐AKTser473/AKT ratio (P = 0.06). In addition, AET decreased HDAC4 expression (P = 0.03; percent changes = −40 ± 19%) and upregulated follistatin (P = 0.01; percent changes = 174 ± 58%), MEF2C (P = 0.05; percent changes = 34 ± 15%), and MyoD expression (P = 0.05; percent changes = 47 ± 18%). AET also increased muscle cross‐sectional area (P = 0.01). AET and IMT increased LBF, functional capacity, and quality of life. Further analyses showed a significant correlation between percent changes in microRNA‐1 and percent changes in follistatin mRNA (P = 0.001, rho = 0.58) and between percent changes in follistatin mRNA and percent changes in peak VO2 (P = 0.004, rho = 0.51). Conclusions AET upregulates microRNA‐1 levels and decreases the protein expression of PTEN, which reduces the inhibitory action on the PI3K‐AKT pathway that regulates the skeletal muscle tropism. The increased levels of microRNA‐1 also decreased HDAC4 and increased MEF2c, MyoD, and follistatin expression, improving skeletal muscle regeneration. These changes associated with the increase in muscle cross‐sectional area and LBF contribute to the attenuation in skeletal myopathy, and the improvement in functional capacity and quality of life in patients with HFrEF. IMT caused no changes in microRNA‐1 and in the downstream‐associated pathway. The increased functional capacity provoked by IMT seems to be associated with amelioration in the respiratory function instead of changes in skeletal muscle. http://ClinicalTrials.gov (Identifier: NCT01747395)

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.

Objective: To evaluate the effects of aerobic exercise training (AET) on cardiac miRNA-16 levels and its target gene VEGF related to microvascular rarefaction in obese Zucker rats (OZR). Methods: OZR (n = 11) and lean (L; n = 10) male rats were assigned into 4 groups: OZR, trained OZR (OZRT), L and trained L (LT). Swimming exercise training lasted 60 min, 1×/day/10 weeks, with 4% body weight workload. Cardiac angiogenesis was assessed by histological analysis (periodic acid-Schiff) by calculating the capillary/fiber ratio. The protein expressions of VEGF, VEGFR2, and CD31 were evaluated by western blot. The expression of miRNA-16 was evaluated by real-time PCR. Results: Heart rate decreased in the trained groups compared to sedentary groups. The cardiac capillary/fiber ratio was reduced in OZR compared to L, LT and OZRT groups, indicating that aerobic exercise training (AET) was capable of reversing the microvascular rarefaction in the obese animals. miRNA-16 expression was increased in OZR compared to L, LT and OZRT. In contrast, its target, VEGF protein expression was 24% lower in OZR compared to L group, which has been normalized in OZRT group. VEGFR2 protein expression was increased in trained groups compared to their controls. CD31, a endothelial cells marker, showed increased expression in OZRT compared to OZR, indicating greater vascularization in OZRT group. Conclusion: AET induced cardiac angiogenesis in obese animals. This revascularization is associated with a decrease in miRNA-16 expression permissive for increased VEGF protein expression, suggesting a mechanism for potential therapeutic application in vascular diseases.

Obesity is a worldwide epidemic affecting over 13% of the adult population and is defined by an excess of body fat that predisposes comorbidities. It is considered a multifactorial disease in which environmental and genetic factors interact, and it is a risk marker for cardiovascular disease. Lifestyle modifications remain the mainstay of treatment for obesity based on adequate diet and physical exercise. In addition, obesity is related to cardiovascular and skeletal muscle disorders, such as cardiac hypertrophy, microvascular rarefaction, and skeletal muscle atrophy. The discovery of obesity-involved molecular pathways is an important step to improve both the prevention and management of this disease. MicroRNAs (miRNAs) are a class of gene regulators which bind most commonly, but not exclusively, to the 3′-untranslated regions of messenger RNAs of protein-coding genes and negatively regulate their expression. Considerable effort has been made to identify miRNAs and target genes that predispose to obesity. Besides their intracellular function, recent studies have demonstrated that miRNAs can be exported or released by cells and circulate within the blood in a remarkably stable form. The discovery of circulating miRNAs opens up intriguing possibilities for the use of circulating miRNA patterns as biomarkers for obesity and cardiovascular diseases. The aim of this review is to provide an overview of the recent discoveries of the role played by miRNAs in the obese phenotype and associated comorbidities. Furthermore, we will discuss the role of exercise training on regulating miRNAs, indicating the mechanisms related to these alterations.

Recognition of the lesion shape by volumetric analysis can provide the surgical team with clearer information, thereby helping in surgical planning and consequently increasing the chances of surgical success.