RESUMO
BACKGROUND: Pericytes are capillary-associated mural cells involved in the maintenance and stability of the vascular network. Although aging is one of the main risk factors for cardiovascular disease, the consequences of aging on cardiac pericytes are unknown. METHODS: In this study, we have combined single-nucleus RNA sequencing and histological analysis to determine the effects of aging on cardiac pericytes. Furthermore, we have conducted in vivo and in vitro analysis of RGS5 (regulator of G-protein signaling 5) loss of function and finally have performed pericytes-fibroblasts coculture studies to understand the effect of RGS5 deletion in pericytes on the neighboring fibroblasts. RESULTS: Aging reduced the pericyte area and capillary coverage in the murine heart. Single-nucleus RNA sequencing analysis further revealed that the expression of Rgs5 was reduced in cardiac pericytes from aged mice. In vivo and in vitro studies showed that the deletion of RGS5 impaired cardiac function, induced fibrosis, and morphological changes in pericytes characterized by a profibrotic gene expression signature and the expression of different ECM (extracellular matrix) components and growth factors, for example, TGFB2 and PDGFB. Indeed, culturing fibroblasts with the supernatant of RGS5-deficient pericytes induced their activation as evidenced by the increased expression of αSMA (alpha smooth muscle actin) in a TGFß (transforming growth factor beta)2-dependent mechanism. CONCLUSIONS: Our results have identified RGS5 as a crucial regulator of pericyte function during cardiac aging. The deletion of RGS5 causes cardiac dysfunction and induces myocardial fibrosis, one of the hallmarks of cardiac aging.
Assuntos
Fibroblastos , Fibrose , Pericitos , Proteínas RGS , Pericitos/metabolismo , Pericitos/patologia , Animais , Proteínas RGS/genética , Proteínas RGS/metabolismo , Proteínas RGS/deficiência , Fibroblastos/metabolismo , Fibroblastos/patologia , Camundongos , Células Cultivadas , Envelhecimento/metabolismo , Envelhecimento/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miocárdio/metabolismo , Miocárdio/patologia , Masculino , Técnicas de CoculturaRESUMO
The objective of this study was to evaluate the sensibility and resistance profiles to antibiotics of pathogens isolated in a hospital unit of food and nutrition. It was evaluated as sample spots, with repetitions, environmental samples, utensils, equipment, manipulators' hands and usually diet that would be served to the hospitalized patients. In the evaluated samples, coagulase positive Staphylococcus (CPS) and Gram negative bacillus were enumerated, and also, it was possible to isolate Klebsiella spp and Escherichia coli. The antimicrobial of less efficiency for CPS was oxacillin and penicillin-G, and for Klebsiella spp ampicillin e cephalothin. It should be emphasized that it was found strains multiresistants of CPS, Klebsiella spp and E. coli. The hospital unit of food and nutrition was evaluated as microbiological inadequate in several points, and it was verified resistance profiles to antibiotics of pathogens isolated in this unit.
O objetivo deste estudo foi avaliar os perfis de sensibilidade e resistência a antibióticos de patógenos isolados em uma unidade de alimentação e nutrição hospitalar. Foram analisados como pontos de amostragem, com repetições, de ambientes, de utensílios, de equipamentos, de mãos de manipuladores e de dieta normal a qual seria servida a pacientes hospitalizados. Nas amostras analisadas, Estafilococos coagulase positiva (ECP) e bacilos Gram negativos no ágar Mac Conkey foram enumerados, e Klebsiella spp e Escherichia coli foram isoladas. Os antimicrobianos de menor eficiência para ECP foram oxacilina e penicilina-G e para Klebsiella spp ampicilina e cefalotina. Cabe ressaltar que foram encontradas cepas multirresistentes de ECP, Klebsiella spp e E. coli. A unidade de alimentação e nutrição hospitalar foi avaliada como inadequada do ponto de vista microbiológico em diversos pontos e verificou-se a presença de perfis de resistência a antibióticos de patógenos isolados nesta unidade.
Assuntos
Staphylococcus , Farmacorresistência Bacteriana , Escherichia coli , Serviço Hospitalar de Nutrição , Klebsiella , AntibacterianosRESUMO
ABSTRACT: This study aimed to evaluate the influence of replacing soybean oil with extra virgin coconut oil in normolipidic and hyperlipidic diets, on the lipid metabolism of Wistar rats. In the first stage of the experiment (30 days), 36 rats were divided into 2 groups and fed with a control or a hyperlipidic diet. Six animals from each group were then killed, and the remaining rats were redistributed into 4 new groups: 2 groups remained on the control and hyperlipidic diets, and in the diets of the other 2 groups, the soybean oil was replaced with coconut oil (30 days). At the end of the assay, the biological models were decapitated for blood collection and removal of organs and peritoneal fat. Although the diet intake differed among groups during both stages of the experiment, no differences were noted with regard to weight gain and peritoneal fat. Replacing soybean oil with coconut oil in the rat diet lowered triglyceride and low-density lipoprotein serum concentrations in both groups. Liver parameters, namely, total cholesterol and triacylglycerols, increased with the substitution of soybean oil by coconut oil in the normolipidic diet and decreased in the hyperlipidic diet. Thus, replacing soybean oil by coconut oil may improve serum and liver lipid levels in Wistar rats.
RESUMO: O estudo teve como objetivo avaliar a influência da substituição do óleo de soja por óleo de coco extravirgem em dietas normolipídicas e hiperlipídicas, sobre o metabolismo lipídico de ratos Wistar. Na primeira fase do experimento, 30 dias, 36 ratos foram distribuídos em dois grupos, receberam dieta controle e dieta hiperlipídica. Após eutanásia de seis animais por grupo, os ratos de ambos os grupos foram redistribuídos em quatro novos grupos, dois permaneceram com as dietas controle e hiperlipídica e nos outros dois houve substituição do óleo de soja por óleo de coco (30 dias). Ao final do ensaio, os modelos biológicos foram decapitados, para coleta de sangue, retirada de órgãos e gordura peritoneal. O consumo de dieta foi diferente entre os grupos durante as duas fases do experimento, porém sem diferença no ganho de peso e gordura peritoneal. A substituição, na dieta, do óleo de soja por óleo de coco diminuiu as concentrações séricas de triacilgliceróis e de lipoproteínas de baixa densidade, em ambos os grupos. Os parâmetros hepáticos colesterol total e triacilgliceróis aumentaram com a substituição do óleo de soja por óleo de coco em dieta normolipídica e diminuíram na dieta hiperlipídica. A substituição do óleo de soja por óleo de coco pode ter benefícios com relação aos lipídeos séricos e hepáticos em ratos Wistar.