Hypertrophy of the right ventricle by pulmonary artery banding in rats: a study of structural, functional, and transcriptomics alterations in the right and left ventricles.

Introduction: Right ventricular remodeling with subsequent functional impairment can occur in some clinical conditions in adults and children. The triggering factors, molecular mechanisms, and, especially, the evolution over time are still not well known. Left ventricular (LV) changes associated with right ventricular (RV) remodeling are also poorly understood. Objectives: The study aimed to evaluate RV morphological, functional, and gene expression parameters in rats submitted to pulmonary artery banding compared to control rats, with the temporal evolution of these parameters, and to analyze the influence of RV remodeling by pulmonary artery banding in rats and their controls over time on LV geometry, histology, gene expression, and functional performance. Methods: Healthy 6-week-old male Wistar-EPM rats weighing 170-200 g were included. One day after the echocardiogram, depending on the animals undergoing the pulmonary artery banding (PAB) procedure or not (control group), they were then randomly divided into subgroups according to the follow-up time: 72 h, or 2, 4, 6, or 8 weeks. In each subgroup, the following were conducted: a new echocardiogram, a hemodynamic study, the collection of material for morphological analysis (hypertrophy and fibrosis), and molecular biology (gene expression). The results were presented as the mean ± standard deviation of the mean. A two-way ANOVA and Tukey post-test compared the variables of the subgroups and evolution follow-up times. The adopted significance level was 5%. Results: There was no significant difference among the subgroups in the percentage of water in both the lungs and the liver (the percentage of water in the lungs ranged from 76% to 78% and that of the liver ranged from 67% to 71%). The weight of the right chambers was significantly higher in PAB animals in all subgroups (RV PAB weighed from 0.34 to 0.48 g, and control subjects, from 0.17 to 0.20 g; right atrium (RA) with PAB from 0.09 to 0.14 g; and control subjects from 0.02 to 0.03 g). In the RV of PAB animals, there was a significant increase in myocyte nuclear volume (97 µm3-183.6 µm3) compared to control subjects (34.2 µm3-57.2 µm3), which was more intense in subgroups with shorter PAB follow-up time, and the fibrosis percentage (5.9%-10.4% vs. 0.96%-1.18%) was higher as the PAB follow-up time was longer. In the echocardiography result, there was a significant increase in myocardial thickness in all PAB groups (0.09-0.11 cm compared to control subjects-0.04-0.05 cm), but there was no variation in RV diastolic diameter. From 2 to 8 weeks of PAB, the S-wave (S') (0.031 cm/s and 0.040 cm/s), and fractional area change (FAC) (51%-56%), RV systolic function parameters were significantly lower than those of the respective control subjects (0.040 cm/s to 0.050 cm/s and 61%-67%). Furthermore, higher expression of genes related to hypertrophy and extracellular matrix in the initial subgroups and apoptosis genes in the longer follow-up PAB subgroups were observed in RV. On the other hand, LV weight was not different between animals with and without PAB. The nuclear volume of the PAB animals was greater than that of the control subjects (74 µm3-136 µm3; 40.8 µm3-46.9 µm3), and the percentage of fibrosis was significantly higher in the 4- and 8-week PAB groups (1.2% and 2.2%) compared to the control subjects (0.4% and 0.7%). Echocardiography showed that the diastolic diameter and LV myocardial thickness were not different between PAB animals and control subjects. Measurements of isovolumetric relaxation time and E-wave deceleration time at the echocardiography were different between PAB animals and control subjects in all subgroups, but there were no changes in diastolic function in the hemodynamic study. There was also increased expression of genes related to various functions, particularly hypertrophy. Conclusion: 1) Rats submitted to pulmonary artery banding presented RV remodeling compatible with hypertrophy. Such alterations were mediated by increased gene expression and functional alterations, which coincide with the onset of fibrosis. 2) Structural changes of the RV, such as weight, myocardial thickness, myocyte nuclear volume, and degree of fibrosis, were modified according to the time of exposure to pulmonary artery banding and related to variations in gene expression, highlighting the change from an alpha to a beta pattern from early to late follow-up times. 3) The study suggests that the left ventricle developed histological alterations accompanied by gene expression modifications simultaneously with the alterations found in the right ventricle.

Photobiomodulation Leads to Reduced Oxidative Stress in Rats Submitted to High-Intensity Resistive Exercise.

The aim of this study was to determine whether oxidative stress markers are influenced by low-intensity laser therapy (LLLT) in rats subjected to a high-intensity resistive exercise session (RE). Female Wistar rats divided into three experimental groups (Ctr: control, 4J: LLLT, and RE) and subdivided based on the sampling times (instantly or 24 h postexercise) underwent irradiation with LLLT using three-point transcutaneous method on the hind legs, which was applied to the gastrocnemius muscle at the distal, medial, and proximal points. Laser (4J) or placebo (device off) were carried out 60 sec prior to RE that consisted of four climbs bearing the maximum load with a 2 min time interval between each climb. Lipoperoxidation levels and antioxidant capacity were obtained in muscle. Lipoperoxidation levels were increased (4-HNE and CL markers) instantly post-RE. LLLT prior to RE avoided the increase of the lipid peroxidation levels. Similar results were also notified for oxidation protein assays. The GPx and FRAP activities did not reduce instantly or 24 h after RE. SOD increased 24 h after RE, while CAT activity did not change with RE or LLLT. In conclusion, LLLT prior to RE reduced the oxidative stress markers, as well as, avoided reduction, and still increased the antioxidant capacity.

Comparative analysis of two low-level laser doses on the expression of inflammatory mediators and on neutrophils and macrophages in acute joint inflammation.

Synovial membrane inflammation plays an important role in osteoarthritis (OA) pathophysiology. The synovial tissue of patients with initial OA is characterized by mononuclear cell infiltration and the production of pro-inflammatory cytokines and other mediators of joint injury. The study aims to evaluate the effect of low-level laser therapy (LLLT) at doses of 2 and 4 J on joint inflammation in rats induced by papain through histopathological analysis, differential counts of inflammatory cells; gene expression of IL-1ß, IL-6, and IL-10; and TNF-α protein expression. Male Wistar rats (20) were randomly divided (5 animals each) into a negative control group, an inflammation injury positive control group, a 2-J LLLT group subjected to injury and treated with 2 J of LLLT, and a 4-J LLLT group subjected to injury and treated with 4 J of LLLT. The animals were subjected to joint inflammation (4 % papain solution) and treated with LLLT. On the day of euthanasia, articular lavage was collected and centrifuged. The supernatant was analyzed for TNF-α protein expression by ELISA and IL-1ß, IL-6, and IL-10 mRNA by RT-PCR. The joint tissue was also examined histologically. ANOVA with Tukey's post hoc test was used for comparisons. All data were expressed as means ± S.D. (p < 0.05). Both laser modalities were efficient in reducing cellular inflammation and decreasing the expression of IL-1ß and IL-6. However, the 2-J treatment led to more reduction in TNF-α than the 4-J treatment. A single application of LLLT with 2 J was more efficient in modulating inflammatory mediators and inflammatory cells.

The renin-angiotensin system is upregulated in the cortex and hippocampus of patients with temporal lobe epilepsy related to mesial temporal sclerosis.

PURPOSE: As reported by several authors, angiotensin II (AngII) is a proinflammatory molecule that stimulates the release of inflammatory cytokines and activates nuclear factor kappaB (NFkappaB), being also associated with the increase of cellular oxidative stress. Its production depends on the activity of the angiotensin converting enzyme (ACE) that hydrolyzes the inactive precursor angiotensin I (AngI) into AngII. It has been suggested that AngII underlies the physiopathological mechanisms of several brain disorders such as stroke, bipolar disorder, schizophrenia, and disease. The aim of the present work was to localize and quantify AngII AT1 and AT2 receptors in the cortex and hippocampus of patients with temporal lobe epilepsy related to mesial temporal sclerosis (MTS) submitted to corticoamygdalohippocampectomy for seizure control. METHOD: Immunohistochemistry, Western blot, and real-time PCR techniques were employed to analyze the expression of these receptors. RESULTS: The results showed an upregulation of AngII AT1 receptor as well as its messenger ribonucleic acid (mRNA) expression in the cortex and hippocampus of patients with MTS. In addition, an increased immunoexpression of AngII AT2 receptors was found only in the hippocampus of these patients with no changes in its mRNA levels. DISCUSSION: These data show, for the first time, changes in components of renin-angiotensin system (RAS) that could be implicated in the physiopathology of MTS.