Nephropathy in hypertensive animals is linked to M2 macrophages and increased expression of the YM1/Chi3l3 protein

Macrophages contribute to a continuous increase in blood pressure and kidney damage in hypertension, but their polarization status and the underlying mechanisms have not been clarified. This study revealed an important role for M2 macrophages and the YM1/Chi3l3 protein in hypertensive nephropathy in a mouse model of hypertension. Bone marrow cells were isolated from the femurs and tibia of male FVB/N (control) and transgenic hypertensive animals that overexpressed the rat form of angiotensinogen (TGM(rAOGEN)123, TGM123-FVB/N). The cells were treated with murine M-CSF and subsequently with LPS+IFN-γ to promote their polarization into M1 macrophages and IL-4+IL-13 to trigger the M2 phenotype. We examined the kidneys of TGM123-FVB/N animals to assess macrophage polarization and end-organ damage. mRNA expression was evaluated using real-time PCR, and protein levels were assessed through ELISA, CBA, Western blot, and immunofluorescence. Histology confirmed high levels of renal collagen. Cells stimulated with LPS+IFN-γ in vitro showed no significant difference in the expression of CD86, an M1 marker, compared to cells from the controls or the hypertensive mice. When stimulated with IL-4+IL-13, however, macrophages of the hypertensive group showed a significant increase in CD206 expression, an M2 marker. The M2/M1 ratio reached 288%. Our results indicate that when stimulated in vitro, macrophages from hypertensive mice are predisposed toward polarization to an M2 phenotype. These data support results from the kidneys where we found an increased infiltration of macrophages predominantly polarized to M2 associated with high levels of YM1/Chi3l3 (91,89%), suggesting that YM1/Chi3l3 may be a biomarker of hypertensive nephropathy

Níveis de proteína bruta em dietas para bovinos de corte: consumo, digestibilidade total e desempenho produtivo Crude protein levels in beef cattle diets: intake, total apparent digestibility of nutrients and productive performance

Este estudo foi conduzido para se avaliar os seguintes parâmetros: consumo e digestibilidade total de matéria seca (MS), matéria orgânica (MO), proteína bruta (PB), extrato etéreo (EE), fibra em detergente neutro (FDN) e carboidratos não-fibrosos (CNF), com e sem correção para cinzas e proteína bruta; ganho de peso, rendimento de carcaça; e conversão alimentar, em bovinos de corte, recebendo dietas contendo quatro níveis de proteína bruta (10, 5; 12; 13, 5 e 15%) na base da matéria seca. Foram utilizados 24 novilhos zebuínos, não-castrados, com peso vivo inicial médio de 398, 4 kg, distribuídos em delineamento em blocos casualizados, com quatro tratamentos e seis repetições. O período experimental teve duração de 78 dias, divididos em três períodos de 21 dias após 15 dias de adaptação. A produção fecal foi estimada por meio da fibra em detergente ácido indigestível (FDAi), após um período de incubação in situ de 144 horas. Com exceção do consumo de PB, que aumentou e o EE e CNF, que diminuíram linearmente, o consumo dos demais nutrientes não foi influenciado pelos níveis protéicos das dietas. A digestibilidade aparente total dos nutrientes não foi influenciada pelas dietas, com exceção da PB e do EE, que apresentaram, respectivamente, comportamentos lineares crescente e decrescente com a inclusão de proteína bruta nas dietas. Os ganhos médios diários de peso vivo, o rendimento de carcaça e a conversão alimentar também não foram influenciados pelas dietas, registrando-se, respectivamente, valores médios de 1.074 g/dia, 51, 43% e 10, 01. Recomenda-se, para bovinos de corte na fase de terminação, com peso vivo inicial próximo a 400 kg, a utilização de dietas com 10, 5% de PB.<br>The intake and total apparent digestibility of dry matter (DM), organic matter (OM), crude protein (CP), ether extract (EE), neutral detergent fiber (NDF) and nonfiber carbohydrate (NFC) with and without correction for ashes and crude protein, the weight gain, carcass yield and the food conversion were estimated in beef cattle fed with diets containing four dietary crude protein levels (10.5; 12; 13.5 and 15%), in dry matter base. There were used 24 non-castrated Zebus steers, with initial mean live weight of 398.4 kg, and allotted to randomized blocks design with four treatments and six replications. The experiment lasted 78 days and was divided in three periods of 21 days after 15 days of adaptation. The fecal production was estimated by the indigestible acid detergent fiber (iADF), after in situ incubation period for 144 hours. The dietary protein levels, except for the increased CP and the linearly decreased EE and NFC intakes, did not influence the nutrients intake. The total apparent digestibility of nutrients was not influenced by the diets, except for CP and EE, which presented positive and negative linear relations, respectively, with the inclusion of dietary crude protein. The daily mean gain of live weight, carcass yield and food conversion were not also influenced by the diets, recording means values of 1, 074 g/day, 51.43% and 10.01, respectively. Based on these results, it is recommended the use of 10.5% of CP in the diet for beef cattle, in the termination phase, with initial live weight close to 400 kg