Angiotensin-II activates vascular inflammasome and induces vascular damage.

Angiotensin-II (Ang-II), a major target for treatment of cardiovascular disease, promotes cardiovascular dysfunction by directly modulating structure and function of vascular cells. Inflammasome components are expressed in the vasculature and are activated by specific stimuli. However, whether Ang-II activates the inflammasome in vascular cells or inflammasome activation contributes to Ang-II-induced vascular damage is still not fully elucidated. We tested the hypothesis that Ang-II induces endothelial dysfunction, vascular remodeling, and high blood pressure via inflammasome activation. C57BL6/J wild type (WT) and Caspase-1 knockout (Casp1-/-) mice were infused with vehicle or Ang-II for two weeks (490 ng/Kg/day) to determine whether the inflammasome contributes to vascular damage induced by Ang-II. Rat Aortic Vascular Smooth Muscle cells (RASMC) were used to determine if the interaction between Ang-II and inflammasomes causes migration and proliferation of vascular smooth muscle cells. Ex vivo studies revealed that Ang-II infusion induced vascular oxidative stress, endothelial dysfunction and vascular remodeling in WT mice. Casp1-/- mice were protected against Ang-II-induced vascular injury. In vitro experiments, Ang-II activated the NLRP3 inflammasome in RASMC, i.e. Ang-II increased Caspase-1 (Casp1) activity and cleavage of pro-interleukin (IL)-1ß. MCC950 (NLRP3 receptor antagonist) prevented Ang-II-induced vascular migration and proliferation, but failed to reduce reactive oxygen species production. In conclusion, Ang-II leads to inflammasome activation in the vasculature contributing to endothelial dysfunction and vascular remodeling. Taken together, we place inflammasomes as a possible therapeutic target in conditions associated with increased Ang-II levels.

Cardiac Alterations in Patients with Familial Lipodystrophy.

Familial lipodystrophy is a rare genetic condition in which individuals have, besides metabolic changes and body fat deposits, a type of cardiomyopathy that has not been well studied. Many of the patients develop cardiovascular changes, the most commonly reported in the literature being the expression of a type of hypertrophic cardiomyopathy. This article, presented as a bibliographic review, reviews the clinical and cardiovascular imaging aspects in this scenario of cardiomyopathy in a rare metabolic disease, based on the latest scientific evidence published in the area. Despite the frequent association of congenital lipodystrophy and ventricular hypertrophy described in the literature, the pathophysiological mechanisms of this cardiomyopathy have not yet been definitively elucidated, and new information on cardiac morphological aspects is emerging in the aegis of recent and advanced imaging methods, such as cardiac magnetic resonance.

Cardiac Alterations in Patients with Familial Lipodystrophy / Alterações Cardiovasculares em Pacientes Portadores de Lipodistrofia Familiar

Abstract Familial lipodystrophy is a rare genetic condition in which individuals have, besides metabolic changes and body fat deposits, a type of cardiomyopathy that has not been well studied. Many of the patients develop cardiovascular changes, the most commonly reported in the literature being the expression of a type of hypertrophic cardiomyopathy. This article, presented as a bibliographic review, reviews the clinical and cardiovascular imaging aspects in this scenario of cardiomyopathy in a rare metabolic disease, based on the latest scientific evidence published in the area. Despite the frequent association of congenital lipodystrophy and ventricular hypertrophy described in the literature, the pathophysiological mechanisms of this cardiomyopathy have not yet been definitively elucidated, and new information on cardiac morphological aspects is emerging in the aegis of recent and advanced imaging methods, such as cardiac magnetic resonance.

Resumo A lipodistrofia familiar é uma condição genética rara na qual indivíduos apresentam, além das alterações metabólicas e de depósitos de gordura físicos, um tipo de cardiomiopatia pouco estudada. Muitos dos pacientes desenvolvem alterações cardiovasculares, sendo a mais comumente reportada em literatura, a expressão de um tipo de cardiomiopatia hipertrófica. Este artigo, apresentado como uma revisão bibliográfica, revisa os aspectos clínicos e de imagem cardiovascular neste cenário de cardiomiopatia em doença metabólica rara, com base nas últimas evidências científicas publicadas na área. Apesar da frequente associação de lipodistrofia congênita e hipertrofia ventricular descrita em literatura, os mecanismos fisiopatológicos desta cardiomiopatia ainda não estão definitivamente elucidados, e novas informações do aspecto morfológico cardíaco surgem à égide de recentes e avançados métodos de imagem como a ressonância cardíaca magnética.

NLRP3 Inflammasome Mediates Aldosterone-Induced Vascular Damage.

BACKGROUND: Inflammation is a key feature of aldosterone-induced vascular damage and dysfunction, but molecular mechanisms by which aldosterone triggers inflammation remain unclear. The NLRP3 inflammasome is a pivotal immune sensor that recognizes endogenous danger signals triggering sterile inflammation. METHODS: We analyzed vascular function and inflammatory profile of wild-type (WT), NLRP3 knockout (NLRP3-/-), caspase-1 knockout (Casp-1-/-), and interleukin-1 receptor knockout (IL-1R-/-) mice treated with vehicle or aldosterone (600 µg·kg-1·d-1 for 14 days through osmotic mini-pump) while receiving 1% saline to drink. RESULTS: Here, we show that NLRP3 inflammasome plays a central role in aldosterone-induced vascular dysfunction. Long-term infusion of aldosterone in mice resulted in elevation of plasma interleukin-1ß levels and vascular abnormalities. Mice lacking the IL-1R or the inflammasome components NLRP3 and caspase-1 were protected from aldosterone-induced vascular damage. In vitro, aldosterone stimulated NLRP3-dependent interleukin-1ß secretion by bone marrow-derived macrophages by activating nuclear factor-κB signaling and reactive oxygen species generation. Moreover, chimeric mice reconstituted with NLRP3-deficient hematopoietic cells showed that NLRP3 in immune cells mediates aldosterone-induced vascular damage. In addition, aldosterone increased the expression of NLRP3, active caspase-1, and mature interleukin-1ß in human peripheral blood mononuclear cells. Hypertensive patients with hyperaldosteronism or normal levels of aldosterone exhibited increased activity of NLRP3 inflammasome, suggesting that the effect of hyperaldosteronism on the inflammasome may be mediated through high blood pressure. CONCLUSIONS: Together, these data demonstrate that NLRP3 inflammasome, through activation of IL-1R, is critically involved in the deleterious vascular effects of aldosterone, placing NLRP3 as a potential target for therapeutic interventions in conditions with high aldosterone levels.

Pericardial effusion and cardiac tamponade: clinical manifestation of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

The authors report a case with pericardial effusion and cardiac tamponade as a rare clinical manifestation of chronic graft-versus-host disease in a young man with acute myelogenous leukemia submitted to an allogeneic hematopoietic stem cell transplantation from a related donor.

Pericardial effusion and cardiac tamponade: clinical manifestation of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

The authors report a case with pericardial effusion and cardiac tamponade as a rare clinical manifestation of chronic graft-versus-host disease in a young man with acute myelogenous leukemia submitted to an allogeneic hematopoietic stem cell transplantation from a related donor.

Microestrutura de pêlos-guarda de felídeos Brasileiros: considerações para a identificação de espécies / Guard-hair microstructure of Brazilian felids: considerations for species identification

O exame da microestrutura da cutícula e medula dos pêlos é uma técnica simples e de baixo custo para identificar espécies de mamíferos para uma variedade de aplicações. Foram estudados pêlos-guarda de 66 indivíduos de oito espécies de felídeos brasileiros (Leopardus colocolo, L.geoffroyi, L.pardalis, L.tigrinus, L.wiedii, Panthera onca, Puma concolor, Puma yagouaroundi), através de amostras colhidas de animais anestesiados em zoológicos. A microestrutura dos pêlos-guarda foi analisada e descrita através de impressões cuticulares e preparações medulares, e posteriormente foi feito um teste cego para avaliar a acurácia da identificação específica. Embora tenham sido encontrados caracteres morfológicos distintos para cada espécie, a sutileza destes caracteres e sua sobreposição entre as diferentes espécies resultaram em uma acurácia relativamente baixa (75 por cento). A identificação de pares ou trios de espécies cujos pêlos têm morfologia mais semelhante (Grupo A: L. pardalis, L. tigrinus, L. wiedii; Grupo B: L. colocolo, L. geoffroyi, P. yagouaroundi; Grupo C: P. concolor, P. onca) elevou a acurácia significativamente (91 por cento). A identificação dos felídeos brasileiros através da microestrutura de seus pêlos é desafiadora e requer um exame cuidadoso de caracteres sutis, devendo ser apoiada por outras técnicas mais acuradas e/ou ser limitada principalmente às aplicações que não requerem identificação específica ou que trabalhem em escalas taxonômicas mais amplas.

The analysis of cuticle and medulla hair microstructure is a simple and inexpensive technique to identify mammal species for a variety of applications. We studied the guard-hairs of 66 individuals of eight felid species occurring in Brazil (Leopardus colocolo, L.geoffroyi, L.pardalis, L.tigrinus, L.wiedii, Panthera onca, Puma concolor, Puma yagouaroundi), through hair samples collected from anesthetized zoo animals. The microstructure of the guard-hairs was analyzed and described through cuticle impressions and medulla preparations; a blind test was conducted to evaluate the accuracy of species identification. Although distinctive morphological characters could be identified for each species, the subtlety of these characters and the overlap of features among species resulted in a relatively poor accuracy (75 percent). The identification of pairs or trios of species whose hair has similar morphologies (Group A: L. pardalis, L. tigrinus, L. wiedii; Group B: L. colocolo, L. geoffroyi, P. yagouaroundi; Group C: P. concolor, P. onca) significantly improved accuracy (91 percent). The identification of Brazilian felids through the microstructure of their hair is challenging and requires careful examination of subtle features, and should be complemented by more accurate techniques and/or be limited mostly to applications where high accuracy is not essential or where a broader taxonomic scale is being evaluated.

Regeneraçäo hepática: algumas definiçöes num universo de incertezas / Liver regeneration: some definitions in an universe of doubts

No presente estudo, os autores elaboraram uma extensa abordagem acêrca da regeneraçäo hepática. Aspectos básicos, tais como cinética da resposta regenerativa, fases do processo replicativo e fatores que interferem na magnitude da síntese hepatocelular de DNA foram considerados. Considerou-se ainda as principais alteraçöes na expressäo gênica relacionadas à regeneraçäo hepática e, por fim, um minucioso relato dos principais fatores de crescimento hepático, com suas interaçöes e possíveis mecanismos de açäo