Altered heart cytokine profile and action potential modulation in cardiomyocytes from Mas-deficient mice.

The renin-angiotensin system (RAS) is a key hormonal system. In recent years, the functional analysis of the novel axis of the RAS (ACE2/Ang-(1-7)/Mas receptor) revealed that its activation can become protective against several pathologies, including cardiovascular diseases. Mas knockout mice (Mas-KO) represent an important tool for new investigations. Indeed, extensive biological research has focused on investigating the functional implications of Mas receptor deletion. However, although the Mas receptor was identified in neonatal cardiomyocytes and also in adult ventricular myocytes, only few reports have explored the Ang-(1-7)/Mas signaling directly in cardiomyocytes to date. This study investigated the implication of Mas receptor knockout to the cytokine profile, energy metabolism, and electrical properties of mice-isolated cardiomyocytes. Here, we demonstrated that Mas-KO mice have modulation in some cytokines, such as G-CSF, IL-6, IL-10, and VEGF in the left ventricle. This model also presents increased mitochondrial number in cardiomyocytes and a reduction in the myocyte diameter. Finally, Mas-KO cardiomyocytes have altered action potential modulation after diazoxide challenge. Such electrical finding was different from the data showed for the TGR(A1-7)3292 (TGR) model, which overexpresses Ang-(1-7) in the plasma by 4.5, used by us as a control. Collectively, our findings exemplify the importance of understanding the ACE2/Ang-(1-7)/Mas pathway in cardiomyocytes and heart tissue. The Mas-KO mice model can be considered an important tool for new RAS investigations.

Bone fenestration repair with leukocyte-platelet-rich fibrin after placement of implants in the anterior maxilla: a case report.

Few reports have been published to date on the management of bone fenestration in the anterior maxilla using leukocyte-platelet-rich fibrin (L-PRF) with deproteinized bovine bone mineral allograft (DBBMA). This case report demonstrates the use of L-PRF associated with DBBMA to repair a bone fenestration after the placement of 2 implants in the anterior maxilla. Placement of 2 osseointegrated implants was planned to replace the missing maxillary central incisors of a patient with bone loss in the buccal region. Reverse treatment planning predicted the fenestration of the buccal cortical plate and exposure of the implants. The implants were placed, and fenestration of the buccal cortical bone around the body of the implants occurred as expected. A mixture of L-PRF and DBBMA, mediated by injectable platelet-rich fibrin (a combination sometimes referred to as sticky bone), was positioned to cover the defect. Cone beam computed tomography 6 months after the intervention showed complete coverage of the fenestration with newly formed bone tissue. The use of L-PRF associated with DBBMA efficiently covered the fenestration and promoted new bone formation.

Implications for dental professionals when caring for paediatric patients.

This paper is a narrative review of relevant literature.

Genetic deletion of the alamandine receptor MRGD leads to dilated cardiomyopathy in mice.

We have recently described a new peptide of the renin-angiotensin system, alamandine, a derivative of angiotensin-(1-7). Mas-related G protein-coupled receptor member D (MrgD) was identified as its receptor. Although similar cardioprotective effects of alamandine to those of angiotensin-(1-7) have been described, the significance of this peptide in heart function is still elusive. We aimed to evaluate the functional role of the alamandine receptor MrgD in the heart using MrgD-deficient mice. MrgD was localized in cardiomyocytes by immunofluorescence using confocal microscopy. High-resolution echocardiography was performed in wild-type and MrgD-deficient mice (2 and 12 wk old) under isoflurane anesthesia. Standard B-mode images were obtained in the right and left parasternal long and short axes for morphological and functional assessment and evaluation of cardiac deformation. Additional heart function evaluation was performed using Langendorff isolated heart preparations and inotropic measurements of isolated cardiomyocytes. Immunofluorescence indicated that the MrgD receptor is expressed in cardiomyocytes, mainly in the membrane and perinuclear and nuclear regions. Echocardiography showed left ventricular remodeling and severe dysfunction in MrgD-deficient mice. Strikingly, MrgD-deficient mice presented a pronounced dilated cardiomyopathy with a marked decrease in systolic function. Echocardiographic changes were supported by the data obtained in isolated hearts and inotropic measurements in cardiomyocytes. Our data add new evidence for a major role for alamandine/MrgD in the heart. Furthermore, our results indicate that we have identified a new gene implicated in dilated cardiomyopathy, unveiling a new target for translational approaches aimed to treat heart diseases. NEW & NOTEWORTHY The renin-angiotensin system is a key target for cardiovascular therapy. We have recently identified a new vasodepressor/cardioprotective angiotensin, alamandine. Here, we unmasked a key role for its receptor, Mas-related G protein-coupled receptor member D (MrgD), in heart function. The severe dilated cardiomyopathy observed in MrgD-deficient mice warrants clinical and preclinical studies to unveil its potential use in cardiovascular therapy.

Zygomaticofacial, Zygomaticoorbital, and Zygomaticotemporal Foramina.

This study aimed to assess the anatomical and morphometric characteristics of the main zygomaticofacial (ZFF), zygomaticoorbital (ZOF), and zygomaticotemporal (ZTF) foramina in Brazilian dry skulls. 61, 69, and 42 skulls for ZFF, ZOF, and ZTF were evaluated by a single calibrated examiner for format, transverse and vertical diameters, and distances from the foramina to anatomical landmarks. Paired t test, Wilcoxon test, Pearson and Spearman correlations were used. Circular outline was the predominant format for ZFF and ZTF, while oval format was the most frequent for ZOF. Median distances from ZFF to frontozygomatic and zygomaticomaxillary sutures were higher on right and left sides of the skulls, respectively (P < 0.005). Mean ZOF transverse diameter was significantly higher on the right sides of the skulls and presented positive correlation between sides (P < 0.05). No differences were observed for mean vertical diameter and distance from the ZOF to the inferolateral angle of the orbit (P > 0.05). No significant difference was found for distance from the ZTF to zygomatic arch between sides (P > 0.05), although there was a positive correlation (P < 0.05). Significant differences were found when analyzing the anatomical and morphometric aspects of ZFF, ZOF, and ZTF.

Activation of angiotensin-converting enzyme 2 improves cardiac electrical changes in ventricular repolarization in streptozotocin-induced hyperglycaemic rats.

AIMS: Diabetic patients present a high level of cardiac arrhythmias and risk of cardiac sudden death. The renin-angiotensin system (RAS) plays a key role in diabetes and cardiac diseases. The present study aimed to evaluate whether an angiotensin-converting enzyme 2 (ACE2) activator, diminazene aceturate (DIZE), could improve the streptozotocin (STZ)-induced electrical changes in ventricular repolarization in hyperglycaemic rats. METHODS AND RESULTS: Hyperglycaemia was induced in Wistar male rats with STZ (60 mg/kg/iv). After 4 weeks of STZ injection, rats were daily treated with saline (control) or DIZE (1 mg/kg/gavage) for four consecutive weeks. The cardiac electrical function was evaluated in vivo by electrocardiogram and in vitro by cardiac action potential records in different pacing frequencies. Treatment with DIZE was not able to reverse hyperglycaemia nor body weight loss. However, DIZE reversed hyperglycaemia-induced cardiac electrical changes in ventricular repolarization. Specifically, animals treated with DIZE showed shorter QT and QTc intervals. In addition, ACE2 activation was capable to shorten the cardiac action potential and also reverse the arrhythmic markers. Diminazene aceturate treatment did not induce arrhythmic events in normal, as well as in hyperglycaemic animals. CONCLUSION: Our data indicate that activation of ACE2 has a beneficial effect in hyperglycaemic rats, improving the cardiac electrical function. Thus, DIZE represents a promising new therapeutic agent to treat hyperglycaemia-induced cardiac electrical changes in ventricular repolarization.

Leadership through a gender lens: Disparities in Dental Research.

This study aimed to analyze the 100 most-cited papers in Dentistry, with a focus on female leadership in dental research. Papers were retrieved from the Web of Science Core Collection (WoS- CC) in the category 'Dentistry, Oral Surgery & Medicine'. Gender was assessed through WoS-CC, Scopus, ResearchGate, social media, institutional websites, and software that assigns gender according to first names (https://genderapi.io). Characteristics of authors in leadership roles were retrieved, such as affiliation, publication history, citations, H factor, and i500. The 100 most-cited papers in Dentistry were authored by 394 researchers, 326 (82.7%) men, and 68 (17.3%) women - there were 4.8 male authors for each female. Among the lead authors, there were 11.3 males for each female. Among female senior authors, there were 7 males for each female. Among lead/senior authors of the 100 most-cited papers (first and last authors, respectively), 18 were women. There was an increase in the participation of women in the top cited papers regardless of authorship role across the six decades, with a peak of two female authors in the first decade of the 21st century. For female authors in leadership roles, their publication history shows the time between their first and last papers in WoS-CC ranged from 4 to 42 years for lead authors and 1 to 39 years for senior authors. Women were found to be largely underrepresented as leaders of the 100 most-cited papers, highlighting pervasive gender inequalities in dental research publications.

Exposure to and infection by Leishmania infantum among domestic dogs in an area of the Cerrado biome, Maranhão, Brazil.

Visceral Leishmaniasis is a serious public health problem and dogs are considered to be the main source of infection in urban areas. In Brazil, this disease is present in all regions, but with high concentration of cases in the Northeast, and the state of Maranhão is considered to be an endemic region. The aim of this study was to conduct an epidemiological, spatial, molecular and serological survey on Leishmania infantum among domestic dogs in the municipality of Belágua, Maranhão. Blood samples were collected from dogs and questionnaires were applied to their owners to obtain epidemiological data and risk factors relating to this zoonosis in the region. The coordinates of the dogs' homes were obtained to produce a disease risk map. Serological diagnoses were made using the indirect immunofluorescence reaction (IFAT) and the dual-path platform chromatographic immunoassay test (DPP®) (Bio-Manguinhos/FIOCRUZ, Brazil). A molecular investigation was undertaken using the polymerase chain reaction (PCR). Georeferencing was performed using the global positioning system (GPS) and cases of canine visceral leishmaniasis in the municipality were spatially represented and analyzed using QGIS version 3.16.6 (QGIS Development Team, 2021). A total of 205 blood samples were collected, of which 122 (59.51%) were seroreactive for L. infantum through IFAT, while the DPP test showed 84 reactive samples (40.97%). IFAT and DPP detected 16 positive animals simultaneously. One sample that was seroreactive through IFAT was also positive through PCR. In the clinical evaluation, it was observed that among the seropositive dogs, 112 (91.80%) were symptomatic and 10 (8.20%) were asymptomatic. In the spatial analysis, the Kernel density estimator enabled determination of the place at greatest risk of occurrence of the disease. The areas with the highest concentrations of cases were in districts with large quantities of precarious housing and lack of basic sanitation. This was the first report on the occurrence of L. infantum among dogs in the municipality of Belágua. The results show that canine visceral leishmaniasis is well dispersed in this municipality, thus putting at risk the human population.

Litomosoides brasiliensis (Nematoda: Onchocercidae) infecting chiropterans in the Legal Amazon region, Brazil.

Chiropterans play an important role in the maintenance of the environmental balance, since they are pollinators, seed dispersers and predators. They contribute to transmission and spreading of microorganisms such as helminths, fungi, protozoa, bacteria and virus. The aim of the present study was to investigate natural filariid infection among bats in the Legal Amazon region, Brazil, by means of parasitological and molecular analyses. Blood samples were collected from 82 bats for blood smears and for DNA extraction via the polymerase chain reaction (PCR) assay. Microfilariae were observed in blood smears from Carollia perspicillata (2), Artibeus lituratus (1), Artibeus fimbriatus (2), Dermanura gnoma (2) and Glossophaga soricina (1). Five positive samples were detected through the PCR assay and four of these were also positive in blood smears. From genome sequencing and comparative analysis with sequences deposited in GenBank, one sample showed 99.31% similarity to the species Litomosoides brasiliensis. The present study expands the geographical distribution of L. brasiliensis, to include the state of Maranhão as an area of occurrence of this species and includes D. gnoma and A. fimbriatus as hosts in Brazil.

Diminazene Aceturate, an angiotensin converting enzyme 2 (ACE2) activator, promotes cardioprotection in ischemia/reperfusion-induced cardiac injury.

This study aimed to investigate whether the Diminazene Aceturate (DIZE), an angiotensin-converting enzyme 2 (ACE2) activator, can revert cardiac dysfunction in ischemia reperfusion-induced (I/R) injury in animals and examine the mechanism underlying this effect. Wistar rats systemically received DIZE (1 mg/kg) for thirty days. Cardiac function in isolated rat hearts was evaluated using the Langendorff technique. After I/R, ventricular non-I/R and I/R samples were used to evaluate ATP levels. Mitochondrial function was assessed using cardiac permeabilized fibers and isolated cardiac mitochondria. Cardiac cellular electrophysiology was evaluated using the patch clamp technique. DIZE protected the heart after I/R from arrhythmia and cardiac dysfunction by preserving ATP levels, independently of any change in coronary flow and heart rate. DIZE improved mitochondrial function, increasing the capacity for generating ATP and reducing proton leak without changing the specific citrate synthase activity. The activation of the ACE2 remodeled cardiac electrical profiles, shortening the cardiac action potential duration at 90 % repolarization. Additionally, cardiomyocytes from DIZE-treated animals exhibited reduced sensibility to diazoxide (KATP agonist) and a higher KATP current compared to the controls. DIZE was able to improve mitochondrial function and modulate cardiac electrical variables with a cardio-protective profile, resulting in direct myocardial cell protection from I/R injury.

Rhipicephalus microplus: An overview of vaccine antigens against the cattle tick.

Rhipicephalus microplus, popularly known as the cattle tick, is the most important tick of livestock as it is responsible for significant economic losses. The use of chemical acaricides is still the most widely used control method despite its known disadvantages. Vaccination would be a safe alternative for the control of R. microplus and holds advantages over the use of chemical acaricides as it is environmental-friendly and leaves no residues in meat or milk. Two vaccines based on the Bm86 protein were commercialized, TickGARD® and Gavac®, with varying reported efficacies in different countries. The use of other vaccines, such as Tick Vac®, Go-Tick®, and Bovimune Ixovac® have been restricted to some countries. Several other proteins have been analyzed as possible antigens for more effective vaccines against R. microplus, including peptidases, serine proteinase inhibitors, glutathione S-transferases, metalloproteases, and ribosomal proteins, with efficacies ranging from 14% to 96%. Nonetheless, more research is needed to develop safe and efficient tick vaccines, such as the evaluation of the efficacy of antigens against other tick species to verify cross-reactivity and inclusion of additional antigens to promote the blocking of the infection and spreading of tick-borne diseases. This review summarizes the discoveries of candidate antigens for R. microplus tick vaccines as well as the methods used to test their efficacy.

Morphometric study of incisive canal and its anatomic variations in brazilian individuals.

Objective: To conduct a morphometric evaluation of the incisive canal, adjacent structures, and their anatomic variations in Brazilian individuals.Methods: A retrospective study was conducted using a sample of 157 multislice computed tomography images of adult Brazilian individuals of both sexes (20-96 years). The exam was performed with the RadiAnt DICOM Viewer 4.0.1 (64-bit) software that uses the DICOM PACS standard for visualization of medical and dental images.Results: The values for length and height of the canal, thickness of the palatine bone plate, and latero-lateral diameter of the incisive foramen were higher in men than in women (p < 0.05).Conclusion: The findings of this study demonstrated morphometric differences for the following parameters: latero-lateral diameter; width of canals at all levels measured; palatine bone plate height; canal length and palatine bone plate thickness in relation to the male and female sexes in the Brazilian population.

Prevalence and characterization of maxillary sinus septa in a brazilian population.

BACKGROUND: The aim of this study was to assess the anatomic aspects of the maxillary sinus septa, by means of computed tomography images, in a Brazilian population. The results might be of clinical significance in sinus lift surgery planning. MATERIAL AND METHODS: In the study, 123 computed tomographs obtained from a private radiology clinic were used. They were analyzed by a single, trained and calibrated observer in order to evaluate the presence, quantity, localizations, dimensions, orientations and different characteristics in dentate, partially edentulous and completely edentulous individuals of the sinus septa. RESULTS: Of the individuals analyzed, 26% had a septum in the maxillary sinus, with 59.6% being classified as complete, 44.2% showed prevalence for the middle region of the maxillary sinus. There was no statistically significant difference between the right and left sides (p>0.05). CONCLUSIONS: The majority of patients in the sample analyzed presented to septa in the maxillary sinuses, and when septa were present, a higher number of occurrence was noted in the middle region of the maxillary sinus. (This region is normally the choice of sinus lift surgery). There was no predilection relative to age, sex and type of dentition. Key words:Multislice computed tomography, maxillary antrum, anatomic variation.

Nanohybrid composed of graphene oxide functionalized with sodium hyaluronate accelerates bone healing in the tibia of rats.

This study synthesized and characterized a nanohybrid composed of graphene oxide (GO) functionalized with sodium hyaluronate (HY) (GO-HY), evaluated its effect in vitro and determined its osteogenic potential in vivo. The synthesized nanohybrid was analyzed by Scanning electron microscopy (SEM), Raman spectrometry, Thermogravimetry, Fourier-transform infrared (FTIR) spectroscopy and X-ray diffraction. MC3T3-E1 cell viability was assessed by MTT assay in 48 and 72 h. Bone defects were created in tibia of 40 Wistar rats and filled with blood clot (control), 1% HY, GO (50, 100 and 200 µg/mL) and the nanohybrid (50, 100 and 200 µg/mL). After 7 and 14 days, histomorphometric analysis was carried out to assess osteogenic potential of the nanohybrid. Immunohistochemical analysis evaluated the expression of vascular endothelial growth factor (VEGF) in bone defects. Thermogravimetric analysis, Raman and FTIR spectrometry confirmed the functionalization of GO with HY by covalent bonds. Five µg/mL concentrations of the nanohybrid did not alter the viability of the MC3T3-E1 cells. Histomorphometric analysis demonstrated that the nanohybrid at 100 µg/mL significantly accelerated the bone repair in tibia of rats when compared to controls (p < 0.01). Immunohistochemical analysis showed a significantly less intense VEGF expression in tibia treated with the nanohybrid when compared to controls (p < 0.05). The nanohybrid composed of GO functionalized with HY was able to induce the acceleration of the tissue regeneration process in bone defects created in the tibia of rats. This novel nanohybrid is a promising material for the field of bone tissue engineering.

Leadership through a gender lens: Disparities in Dental Research

Abstract This study aimed to analyze the 100 most-cited papers in Dentistry, with a focus on female leadership in dental research. Papers were retrieved from the Web of Science Core Collection (WoS- CC) in the category 'Dentistry, Oral Surgery & Medicine'. Gender was assessed through WoS-CC, Scopus, ResearchGate, social media, institutional websites, and software that assigns gender according to first names (https://genderapi.io). Characteristics of authors in leadership roles were retrieved, such as affiliation, publication history, citations, H factor, and i500. The 100 most-cited papers in Dentistry were authored by 394 researchers, 326 (82.7%) men, and 68 (17.3%) women - there were 4.8 male authors for each female. Among the lead authors, there were 11.3 males for each female. Among female senior authors, there were 7 males for each female. Among lead/senior authors of the 100 most-cited papers (first and last authors, respectively), 18 were women. There was an increase in the participation of women in the top cited papers regardless of authorship role across the six decades, with a peak of two female authors in the first decade of the 21st century. For female authors in leadership roles, their publication history shows the time between their first and last papers in WoS-CC ranged from 4 to 42 years for lead authors and 1 to 39 years for senior authors. Women were found to be largely underrepresented as leaders of the 100 most-cited papers, highlighting pervasive gender inequalities in dental research publications.

Resumo Objetivou-se analisar os 100 artigos mais citados em Odontologia, com foco na liderança feminina na pesquisa odontológica. Os artigos foram identificados utilizando-se a base de dados Web of Science Core Collection (WoS-CC) na categoria 'Dentistry, Oral Surgery & Medicine'. O gênero dos autores foi avaliado por meio do WoS-CC, Scopus, ResearchGate, mídias sociais, sites institucionais e um software que atribui gênero de acordo com o primeiro nome (https://genderapi.io). As características dos autores em papéis de liderança foram identificadas, como afiliação, histórico de publicação, número de citações, fator H e i500. Os 100 trabalhos mais citados em Odontologia foram de autoria de 394 pesquisadores, sendo 326 (82,7%) homens e 68 (17,3%) mulheres - foram 4,8 autores homens para cada mulher. Entre os primeiros autores, havia 11,3 homens para cada mulher. Entre os últimos autores, havia 7 homens para cada mulher. Entre os primeiros/últimos autores dos 100 artigos mais citados, 18 eram mulheres. Houve um aumento na participação de mulheres nos artigos mais citados, independentemente do papel da autoria ao longo das seis décadas, com um pico de duas autoras na primeira década do século XXI. Para autoras em papéis de liderança, seu histórico de publicação mostra que o tempo entre o primeiro e o último artigo no WoS-CC variou de 4 a 42 anos para primeiro autor principais e de 1 a 39 anos para último autor. Verificou-se que as mulheres estão sub-representadas como líderes dos 100 artigos mais citados, destacando-se desigualdades de gênero generalizadas nas publicações em pesquisa odontológica.

Malocclusion negatively impacted the oral health-related quality of life of children of low socioeconomic status / Maloclusão impactou negativamente a qualidade de vida relacionada à saúde bucal de crianças de baixo nível socioeconômico

Aim: This study assessed whether the presence of malocclusion had a negative impact on the oral health-related quality of life (OHRQoL) of eight to ten-year-old children of low socioeconomic status. Methods: A cross-sectional study was conducted with a total of 111 children, eight to ten years of age, randomly selected from public schools from Diamantina, MG, Brazil. The number of children was determined by a sample size calculation. Two calibrated examiners performed clinical oral examinations for the diagnosis of malocclusion, dental caries experience, and traumatic dental injuries following the Dental Aesthetic Index (DAI), the World Health Organization (WHO), and Andreasen's classification, respectively. The Brazilian version of the Child Perceptions Questionnaire (CPQ8-10) was applied to evaluate the OHRQoL. Descriptive and bivariate (p < 0.05) analyses were also performed. Results: Children had a mean age of 8.89 ± 0.82 years, of which 52.3% were female. The prevalence of malocclusion was 62.2%. Significant differences were found in emotional (p = 0.045) and social (p = 0.017) well-being subscale scores as well as in the total CPQ8-10 (p = 0.022) scores between children with and without malocclusion. Conclusion: The presence of malocclusion negatively impacted the OHRQoL of children aged eight to ten years of age of a low socioeconomic status.

Objetivo: Este estudo avaliou se a presença de maloclusão impactou negativamente a qualidade de vida relacionada à saúde bucal (QVRSB) de crianças de oito a dez anos de idade de baixo nível socioeconômico.Métodos: Um estudo transversal foi conduzido com um total de 111 crianças de oito a dez anos de idade selecionadas aleatoriamente em escolas públicas de Diamantina, Brasil. O número de crianças foi determinado por cálculo amostral. Dois examinadores calibrados realizaram exames clínicos bucais para o diagnóstico de maloclusão, experiência de cárie dentária e lesões dentárias traumáticas após o Índice de Estética Dental (DAI), Organização Mundial da Saúde (OMS) e classificação de Andreasen, respectivamente. A versão brasileira do Child Perceptions Questionnaire (CPQ8-10) foi aplicada para avaliar a QVRSB. Foram realizadas análises descritivas e bivariadas (p < 0,05). Resultados: As crianças tinham média de idade de 8,89 ± 0,82 anos, sendo 52,3% do sexo feminino. A prevalência de maloclusão foi de 62,2%. Foram encontradas diferenças significativas nos escores das subescalas de bem-estar emocional (p = 0,045) e social (p = 0,017), como também nos escores totais do CPQ8-10 (p = 0,022) entre crianças com e sem maloclusão. Conclusão: A presença de maloclusão impactou negativamente a QVRSB de crianças de oito a dez anos de idade de baixo nível socioeconômico.

Antidepressant-like and anxiolytic-like effects of cannabidiol: a chemical compound of Cannabis sativa.

Anxiety and depression are pathologies that affect human beings in many aspects of life, including social life, productivity and health. Cannabidiol (CBD) is a constituent non-psychotomimetic of Cannabis sativa with great psychiatric potential, including uses as an antidepressant-like and anxiolytic-like compound. The aim of this study is to review studies of animal models using CBD as an anxiolytic-like and antidepressant-like compound. Studies involving animal models, performing a variety of experiments on the above-mentioned disorders, such as the forced swimming test (FST), elevated plus maze (EPM) and Vogel conflict test (VCT), suggest that CBD exhibited an anti-anxiety and antidepressant effects in animal models discussed. Experiments with CBD demonstrated non-activation of neuroreceptors CB1 and CB2. Most of the studies demonstrated a good interaction between CBD and the 5-HT1A neuro-receptor.

Cardiovascular effects of angiotensin A: a novel peptide of the renin-angiotensin system.

INTRODUCTION: Angiotensin (Ang) A was first identified in human plasma and it differs from Ang II in Ala(1) instead of Asp(1). Here, we hypothesized that the actions of this peptide might explain, at least partially, the limited effects of AT1R antagonists in certain cardiovascular diseases. MATERIALS AND METHODS: The effects of Ang A and Ang II on blood pressure (BP) and heart function were compared. Importantly, participation of AT1R in these effects was evaluated. Furthermore, the effects of these two peptides on ischemia/reperfusion arrhythmias and involvement of calcium in these effects were investigated. RESULTS: Administration of increasing doses of these peptides caused elevations in BP at comparable magnitude. AT1R blockade completely abolished these effects. The actions of these peptides in cardiac function were quite similar although the effects of Ang A were only partially blocked by losartan. Interestingly, Ang II elicited an increase in the duration of ischemia/reperfusion arrhythmias while Ang A had no effect on cardiac rhythm during reperfusion. In accordance, differently to Ang II, Ang A did not induce any significant effect on calcium transient during baseline and ischemic stress conditions. CONCLUSIONS: These data suggest that the existence of alternative peptides of the renin-angiotensin system (RAS) might contribute to the limited effects of angiotensin receptor blockers (ARBs) in certain pathophysiological circumstances.

Bone marrow mesenchymal stromal cells rescue cardiac function in streptozotocin-induced diabetic rats.

OBJECTIVES: In the present study, we investigated whether MSC-transplantation can revert cardiac dysfunction in streptozotocin-induced diabetic rats and the immunoregulatory effects of MSC were examined. BACKGROUND: Cardiac complications are one of the main causes of death in diabetes. Several studies have shown anti-diabetic effects of bone marrow mesenchymal stromal cells (MSC). METHODS/RESULTS: The rats were divided in three groups: Non-diabetic, Diabetic and Diabetic-Treated with 5 × 10(6) MSC 4 weeks after establishment of diabetes. Four weeks after MSC-therapy, systemic metabolic parameters, immunological profile and cardiac function were assessed. MSC-transplantation was able to revert the hyperglycemia and body weight loss of the animals. In addition, after MSC-transplantation a decrease in corticosterone and IFN-γ sera levels without restoration of insulin and leptin plasma levels was observed. Also, MSC-therapy improved electrical remodeling, shortening QT and QTc in the ECG and action potential duration of left ventricular myocytes. No arrhythmic events were observed after MSC-transplantation. MSC-therapy rescued the cardiac beta-adrenergic sensitivity by increasing beta-1 adrenergic receptor expression. Both alpha and beta cardiac AMPK and p-AMPK returned to baseline values after MSC-therapy. However, total ERK1 and p-ERK1/2 were not different among groups. CONCLUSION: The results indicate that MSC-therapy was able to rescue cardiac impairment induced by diabetes, normalize cardiac AMPK subunit expression and activity, decrease corticosterone and glycemia and exert systemic immunoregulation.

The cardiac expression of Mas receptor is responsive to different physiological and pathological stimuli.

The Mas protooncogene encodes a G protein-coupled receptor that has been described as a functional receptor for the cardioprotective fragment of the renin-angiotensin system (RAS), Angiotensin (Ang)-(1-7). The aim of this current study was to evaluate the responsiveness of Mas expression in hearts during different physiological and pathological conditions in rats. Physical training was considered a physiological condition, while isoproterenol-induced hypertrophy, myocardial infarction and DOCA-salt model of hypertension were used as pathological models of heart injury. The expression of Mas was analyzed by western blotting. Although swim-trained rats presented significant cardiac hypertrophy, our physical training protocol was unable to induce changes in the expression of Mas. On the other hand, cardiac hypertrophy and damage elicited by isoproterenol treatment led to a reduction in Mas expression. Myocardial infarction also significantly decreased the expression of Mas after 21 days of myocardial ischemia. Additionally, Mas expression levels were increased in hearts of DOCA-salt rats. Our present data indicate that Mas expression is responsive to different pathological stimuli, thereby suggesting that Mas receptor is involved in the homeostasis of the heart, as well as in the establishment and progression of cardiac diseases.