Our objective was to analyze the effect of spironolactone on cardiac remodeling after experimental myocardial infarction (MI), assessed by matricellular proteins levels, cardiac collagen amount and ...distribution, myocardial tissue metalloproteinase inhibitor-1 (TIMP-1) concentration, myocyte hypertrophy, left ventricular architecture, and in vitro and in vivo cardiac function.
Wistar rats were assigned to 4 groups: control group, in which animals were submitted to simulated surgery (SHAM group; n=9); group that received spironolactone and in which animals were submitted to simulated surgery (SHAM-S group, n=9); myocardial infarction group, in which animals were submitted to coronary artery ligation (MI group, n=15); and myocardial infarction group with spironolactone supplementation (MI-S group, n=15). The rats were observed for 3 months.
The MI group had higher values of left cardiac chambers and mass index and lower relative wall thicknesses compared with the SHAM group. In addition, diastolic and systolic functions were worse in the MI groups. However, spironolactone did not influence any of these variables. The MI-S group had a lower myocardial hydroxyproline concentration and myocyte cross-sectional area compared with the MI group. Myocardial periostin and collagen type III were lower in the MI-S group compared with the MI-group. In addition, TIMP-1 concentration in myocardium was higher in the MI-S group compared with the MI group.
The predominant consequence of spironolactone supplementation after MI is related to reductions in collagens, with discrete attenuation of other remodeling variables. Importantly, this effect may be modulated by periostin and TIMP-1 levels.
Cardiovascular disease is a leading cause of death worldwide. Heart failure is a cardiovascular disease with high prevalence, morbidity, and mortality. Several natural compounds have been studied for ...attenuating pathological cardiac remodeling. Orange juice has been associated with cardiovascular disease prevention by attenuating oxidative stress. However, most studies have evaluated isolated phytochemicals rather than whole orange juice and usually under pathological conditions. In this study, we evaluated plasma metabolomics in healthy rats receiving Pera or Moro orange juice to identify possible metabolic pathways and their effects on the heart. Methods: Sixty male Wistar rats were allocated into 3 groups: control (C), Pera orange juice (PO), and Moro orange juice (MO). PO and MO groups received Pera orange juice or Moro orange juice, respectively, and C received water with maltodextrin (100 g/L). Echocardiogram and euthanasia were performed after 4 weeks. Plasma metabolomic analysis was performed by high-resolution mass spectrometry. Type I collagen was evaluated in picrosirius red-stained slides and matrix metalloproteinase (MMP)-2 activity by zymography. MMP-9, tissue inhibitor of metalloproteinase (TIMP)-2, TIMP-4, type I collagen, and TNF-α protein expression were evaluated by Western blotting. Results: We differentially identified three metabolites in PO (N-docosahexaenoyl-phenylalanine, diglyceride, and phosphatidylethanolamine) and six in MO (N-formylmaleamic acid, N2-acetyl-L-ornithine, casegravol isovalerate, abscisic alcohol 11-glucoside, cyclic phosphatidic acid, and torvoside C), compared to controls, which are recognized for their possible roles in cardiac remodeling, such as extracellular matrix regulation, inflammation, oxidative stress, and membrane integrity. Cardiac function, collagen level, MMP-2 activity, and MMP-9, TIMP-2, TIMP-4, type I collagen, and TNF-α protein expression did not differ between groups. Conclusion: Ingestion of Pera and Moro orange juice induces changes in plasma metabolites related to the regulation of extracellular matrix, inflammation, oxidative stress, and membrane integrity in healthy rats. Moro orange juice induces a larger number of differentially expressed metabolites than Pera orange juice. Alterations in plasma metabolomics induced by both orange juice are not associated with modifications in cardiac extracellular matrix components. Our results allow us to postulate that orange juice may have beneficial effects on pathological cardiac remodeling.
Methionine is an essential amino acid involved in critical metabolic process, and regulation of methionine flux through metabolism is important to supply this amino acid for cell needs. Elevation in ...plasma methionine commonly occurs due to mutations in methionine-metabolizing enzymes, such as methionine adenosyltransferase. Hypermethioninemic patients exhibit clinical manifestations, including neuronal and liver disorders involving inflammation and tissue injury, which pathophysiology is not completely established. Here, we hypothesize that alterations in macrophage inflammatory response may contribute to deleterious effects of hypermethioninemia. To this end, macrophage primary cultures were exposed to methionine (1 mM) and/or its metabolite methionine sulfoxide (0.5 mM), and M1/proinflammatory or M2/anti-inflammatory macrophage polarization was evaluated. In addition, inflammation-related pathways including oxidative stress parameters, as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities; reactive oxygen species (ROS) production, and purinergic signaling, as ATP/ADP/AMPase activities, were investigated. Methionine and/or methionine sulfoxide induced M1/classical macrophage activation, which is related to proinflammatory responses characterized by increased iNOS activity and TNF-α release. Further experiments showed that treatments promoted alterations on redox state of macrophages by differentially modulated SOD and CAT activities and ROS levels. Finally, methionine and/or methionine sulfoxide treatment also altered the extracellular nucleotide metabolism, promoting an increase of ATPase/ADPase activities in macrophages. In conclusion, these findings contribute to better understand the participation of proinflammatory responses in cell injury observed in hypermethioninemic patients.
Composed of two main forest formations, Ombrophilous Forest and Seasonal Forest, the Brazilian Atlantic Forest biome is constituted currently by a mosaic of forest remnants and secondary vegetation. ...Representatives of the Ponerinae ant genus Neoponera are observed mainly in both wet and seasonally dry forests. The aim of this study was to approach the diversity of the genus Neoponera in the north of the Atlantic Forest of Brazil (from the extreme north of its distribution to the Doce River hydrographic basin in the south), associating the occurrence of ant species with the types of vegetation. We have compiled occurrence data from the collection of the Myrmecology Laboratory of the Cocoa Research Center, on internet, or available in literature. We found information on 23 species of Neoponera, including a new record for the Atlantic Forest, Neoponera globularia (Mackay & Mackay, 2010), and a new record for Brazil, Neoponera fiebrigi Forel, 1912. The relative composition of the Neoponera assemblages was evaluated according to the types of vegetation. We found that the occurrence of the genus Neoponera is mainly related to the types of vegetation of the focus region, principally dense forests where a higher diversity was observed.
After acute myocardial infarction, during the cardiac repair phase, periostin is released into the infarct and activates signaling pathways that are essential for the reparative process. However, the ...role of periostin in chronic cardiac remodeling after myocardial infarction remains to be elucidated. Therefore, the objective of this study was to investigate the relationship between tissue periostin and cardiac variables in the chronic cardiac remodeling induced by myocardial infarction.
Male Wistar rats were assigned to 2 groups: a simulated surgery group (SHAM; n = 8) and a myocardial infarction group (myocardial infarction; n = 13). After 3 months, morphological, functional and biochemical analyses were performed. The data are expressed as means±SD or medians (including the lower and upper quartiles).
Myocardial infarctions induced increased left ventricular diastolic and systolic areas associated with a decreased fractional area change and a posterior wall shortening velocity. With regard to the extracellular matrix variables, the myocardial infarction group presented with higher values of periostin and types I and III collagen and higher interstitial collagen volume fractions and myocardial hydroxyproline concentrations. In addition, periostin was positively correlated with type III collagen levels (r = 0.673, p =0.029) and diastolic (r = 0.678, p =0.036) and systolic (r = 0.795, p =0.006) left ventricular areas. Considering the relationship between periostin and the cardiac function variables, periostin was inversely correlated with both the fractional area change (r = -0.783, p =0.008) and the posterior wall shortening velocity (r = -0.767, p =0.012).
Periostin might be a modulator of deleterious cardiac remodeling in the chronic phase after myocardial infarction in rats.
Based on the antioxidant properties of pomegranate, this study was designed to investigate the effects of pomegranate peel extract on damage associated with hypertension and aging in a spontaneously ...hypertensive rat (SHR) model. The influence of pomegranate consumption was examined on systolic blood pressure (SBP), angiotensin-converting enzyme (ACE) coronary activity, oxidative stress, and vascular morphology. Four- or 28-wk-old SHR model rats were treated for 30 d, with terminal experimental animal age being 8 and 32 wk, respectively, with either pomegranate extract (SHR-PG) or filtered water (SHR). Data showed significant reduction in SBP and coronary ACE activity in both age groups. The levels of superoxide anion, a measure of oxidative stress, were significantly lower in animals in the SHR-PG group compared to SHR alone. Coronary morphology demonstrated total increases in vascular wall areas were in the SHR group, and pomegranate peel extract diminished this effect. Pomegranate peel extract consumption conferred protection against hypertension in the SHR model. This finding was demonstrated by marked reduction in coronary ACE activity, oxidative stress, and vascular remodelling. In addition, treatment was able to reduce SBP in both groups. Evidence indicates that the use of pomegranate peel extract may prove beneficial in alleviating coronary heart disease.
Experimental studies have shown the action of green tea in modulating cardiac remodeling. However, the effects of green tea on the cardiac remodeling process induced by doxorubicin (DOX) are not ...known. Therefore, this study is aimed at evaluating whether green tea extract could attenuate DOX-induced cardiac remodeling, assessed by cardiac morphological and functional changes and associated with the evaluation of different modulators of cardiac remodeling. The animals were divided into four groups: the control group (C), the green tea group (GT), the DOX group (D), and the DOX and green tea group (DGT). Groups C and GT received intraperitoneal sterile saline injections, D and DGT received intraperitoneal injections of DOX, and GT and DGT were fed chow supplemented with green tea extract for 35 days prior to DOX injection. After forty-eight hours, we performed an echocardiogram and euthanasia and collected the materials for analysis. Green tea attenuated DOX-induced cardiotoxicity by increasing cardiac function and decreasing the concentric remodeling. Treatment with DOX increased oxidative stress in the heart, marked by a higher level of lipid hydroperoxide (LH) and lower levels of antioxidant enzymes. Treatment with green tea increased the antioxidant enzymes’ activity and decreased the production of LH. Green tea extract increased the expression of Top2-β independent of DOX treatment. The activity of ATP synthase, citrate synthase, and complexes I and II decreased with DOX, without the effects of green tea. Both groups that received DOX presented with a lower ratio of P-akt/T-akt and a higher expression of CD45, TNFα, and intermediate MMP-2, without the effects of green tea. In conclusion, green tea attenuated cardiac remodeling induced by DOX and was associated with increasing the expression of Top2-β and lowering oxidative stress. However, energy metabolism and inflammation probably do not receive the benefits induced by green tea in this model.
Background/Aims: The aim of this study was to evaluate the influence of pamidronate on ventricular remodeling after myocardial infarction. Methods: Male Wistar rats were assigned to four groups: a ...sham group, in which animals were submitted to simulated surgery and received weekly subcutaneous injection of saline (S group; n=14); a group in which animals received weekly subcutaneous injection of pamidronate (3 mg/kg of body weight) and were submitted to simulated surgery (SP group, n=14); a myocardial infarction group, in which animals were submitted to coronary artery ligation and received weekly subcutaneous injection of saline (MI group, n=13); and a myocardial infarction group with pamidronate treatment (MIP group, n=14). The rats were observed for three months. Results: Animals submitted to MI had left chamber enlargement and worse diastolic and systolic function compared with SHAM groups. E/A ratio, LV posterior and relative wall thickness were lower in the MIP compared with the MI group. There was no interaction between pamidronate administration and MI on systolic function, myocyte hypertrophy, collagen content, and calcium handling proteins. Conclusion: Pamidronate attenuates diastolic dysfunction following MI.
Climate change threatens freshwater fish by severely modifying water quality and hydrological dynamics, hence altering the species distribution. We assessed the climate change effects on the ...geographical distribution of
Salminus brasiliensis
, a keystone species of economic interest in the La Plata River basin. Using ecological niche models, we estimated the species range in the present time and assessed the range shift phenomena through climatically suitable areas in the future. We also quantified the predictive uncertainty from niche models, atmosphere–ocean general circulation models, and carbon emission scenarios. Our predictions indicated a great range contraction of
S. brasiliensis
in the future. The south-central portion of the basin should retain the climate refuge function for the species at 2050. Nonetheless, the segregation of this climate refuge in two smaller parts was predicted at the end of the century. Our study also revealed that the greatest source of uncertainty in forecasts of species range shifts arises from using alternative niche algorithms in modeling process. Our results contribute to more effective measures for conservation of
S. brasiliensis
, thus helping to ensure the ecosystem processes and socioeconomic activities in the basin dependent on this species.
Abstract only Introduction: Transcranial direct current stimulation (tDCS) has the potential to improve upper limb motor outcomes after stroke. Objective: To evaluate the safety and preliminary ...efficacy of active cathodal compared to sham tDCS of the primary motor cortex of the unaffected hemisphere (ctDCSM1 UH ), within 72 hours to 6 weeks post-ischemic stroke. Methods: In this randomized, double-blind study, 30 patients with unilateral hand paresis were assigned to either active or sham ctDCSM1 UH as add-on interventions to rehabilitation. The primary outcome was the frequency of adverse events. Secondary outcomes, compared before, immediately after treatment and three months later, included measures of upper limb motor performance and quality of life. Stroke volume was assessed before and after treatment. Results: Overall, tDCS was well tolerated and there were no serious adverse events. One subject in the active group reported paresthesias in the paretic arm during the first session of ctDCSM1 UH . Heart rate increased significantly after active and decreased significantly after sham ctDCSM1 UH but these changes were not clinically significant. Upper limb motor impairment and quality of life improved significantly more in the sham than in the active group at three months post-treatment according to intention-to-treat and per-protocol analyses. The between-group difference in motor impairment was not clinically relevant. There were no recurrent strokes and lesion volumes did not increase significantly in either group. Conclusions: Active ctDCSM1 UH was safe and well tolerated but the preliminary efficacy results do not support a beneficial role of this intervention within the first six weeks after stroke.
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