Exogenous 17-β estradiol administration blunts progression of established angiotensin II-induced abdominal aortic aneurysms in female ovariectomized mice

BACKGROUND: Abdominal aortic aneurysms (AAAs) occur predominately in males. However, AAAs in females have rapid growth rates and rupture at smaller sizes. Mechanisms contributing to AAA progression in females are undefined. We defined effects of ovariectomy, with and without 17-β estradiol (E2), on progression of established angiotensin II (AngII)-induced AAAs in female mice. METHODS: We used neonatal testosterone exposures at 1 day of age to promote susceptibility to AngII-induced AAAs in adult female Ldlr(−/−) mice. Females were infused with AngII for 28 days to induce AAAs, and then stratified into groups that were sham, ovariectomized (Ovx, vehicle), or Ovx with E2 administration for 2 months of continued AngII infusions. Aortic lumen diameters were quantified by ultrasound and analyzed by linear mixed model, and maximal AAA diameters were analyzed by one-way ANOVA. Atherosclerosis was quantified en face in the aortic arch. AAA tissue sections were analyzed for cellular composition. We quantified effects of E2 on abdominal aortic smooth muscle cell (SMC) growth, α-actin and transforming growth factor-beta (TGF-β) production, and wound healing. RESULTS: Serum E2 concentrations were increased significantly by E2. Aortic lumen diameters increased over time in sham-operated and Ovx (vehicle) females, but not in Ovx females administered E2. At day 70, E2 administration decreased significantly aortic lumen diameters compared to Ovx vehicle and sham-operated females. Compared to Ovx females (vehicle), maximal AAA diameters were reduced significantly by E2. AAA tissue sections from Ovx females administered E2 exhibited significant increases in α-actin and decreases in neutrophils compared to Ovx females administered vehicle. In abdominal aortic SMCs, E2 resulted in a concentration-dependent increase in α-actin, elevated TGF-β, and more rapid wound healing. E2 administration to Ovx females also significantly reduced atherosclerotic lesions compared to sham-operated females. This effect was accompanied by significant reductions in serum cholesterol concentrations. CONCLUSIONS: E2 administration to Ovx females abolished progressive growth and decreased severity of AngII-induced AAAs. These effects were accompanied by increased SMC α-actin, elevated TGF-β, and reduced neutrophils. Similarly, E2 administration reduced AngII-induced atherosclerosis. These results suggest that loss of E2 in post-menopausal females may contribute to progressive growth of AAAs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13293-015-0030-1) contains supplementary material, which is available to authorized users

Telocytes and putative stem cells in the lungs: electron microscopy, electron tomography and laser scanning microscopy

This study describes a novel type of interstitial (stromal) cell — telocytes (TCs) — in the human and mouse respiratory tree (terminal and respiratory bronchioles, as well as alveolar ducts). TCs have recently been described in pleura, epicardium, myocardium, endocardium, intestine, uterus, pancreas, mammary gland, etc. (see www.telocytes.com). TCs are cells with specific prolongations called telopodes (Tp), frequently two to three per cell. Tp are very long prolongations (tens up to hundreds of μm) built of alternating thin segments known as podomers (≤ 200 nm, below the resolving power of light microscope) and dilated segments called podoms, which accommodate mitochondria, rough endoplasmic reticulum and caveolae. Tp ramify dichotomously, making a 3-dimensional network with complex homo- and heterocellular junctions. Confocal microscopy reveals that TCs are c-kit- and CD34-positive. Tp release shed vesicles or exosomes, sending macromolecular signals to neighboring cells and eventually modifying their transcriptional activity. At bronchoalveolar junctions, TCs have been observed in close association with putative stem cells (SCs) in the subepithelial stroma. SCs are recognized by their ultrastructure and Sca-1 positivity. Tp surround SCs, forming complex TC-SC niches (TC-SCNs). Electron tomography allows the identification of bridging nanostructures, which connect Tp with SCs. In conclusion, this study shows the presence of TCs in lungs and identifies a TC-SC tandem in subepithelial niches of the bronchiolar tree. In TC-SCNs, the synergy of TCs and SCs may be based on nanocontacts and shed vesicles

Relação entre o perfil antropométrico e bioquímico em crianças e adolescentes com diabetes melito tipo 1 Relación entre perfiles antropométrico y bioquímico en niños y adolescentes con diabetes mellitus tipo 1 Relationship between anthropometric and biochemical profiles in children and adolescents with type 1 diabetes

OBJETIVO: Avaliar a relação entre o perfil antropométrico e bioquímico de crianças e adolescentes com diabetes melito tipo 1 (DM1). MÉTODOS: Estudo transversal com 11 crianças e 43 adolescentes com DM1. Coletaram-se dados socioeconômicos e demográficos (idade, sexo, escolaridade, renda), clínicos (insulinoterapia), antropométricos (peso, estatura, dobras cutâneas, circunferência da cintura - CC) e bioquímicos (hemoglobina glicada - HbA, glicemias casual - GLC, pós-prandial - GLPP, e perfil lipídico). Foram utilizados o teste t de Student (p<0,05) e a correlação de Pearson (p<0,05). RESULTADOS: A renda média per capita foi de 0,58±0,39 salário-mínimo e predominou o esquema de três aplicações de insulina/dia em 72,2% da amostra. A maioria apresentou estatura (92,6%) e IMC (87%) adequados para a idade. Aqueles com índice da HbA (inHbA) adequado apresentaram menores GLC (p=0,002) e GLPP (p<0,001). O inHbA correlacionou-se positivamente com CC (p=0,013), GLC (p=0,014), GLPP (p<0,001), TG e VLDL (p<0,001). CONCLUSÕES: O pior controle glicêmico relaciona-se a maiores níveis de lipídeos séricos e CC mais elevada.<br>OBJETIVO: Evaluar la relación entre perfil antropométrico y bioquímico de niños y adolescentes con diabetes mellitus tipo 1 (DM1). MÉTODOS: Estudio transversal con 11 niños y 43 adolescentes con DM1. Se recogieron datos socioeconómicos y demográficos (edad, sexo, escolaridad, ingresos), clínicos (insulinoterapia), antropométricos (peso, estatura, pliegues cutáneos, circunferencia de la cintura-CC) y bioquímicos (hemoglobina glicada - HbA, glucemias casual - GLC, postprandial - GLPP y perfil lipídico). Se utilizaron la prueba t de Student y la correlación de Pearson (p<0,05). RESULTADOS: El ingreso mediano per capita fue de 0,58±0,39 salario mínimo y predominó el esquema de tres aplicaciones de insulina/día en el 72,2% de la muestra. La mayoría presentó estatura (92,6%) e IMC (87%) adecuados a la edad. Aquellos con índice de HbA (inHbA) adecuado presentaron menores GLC (p=0,002) y GLPP (p<0,001). El inHbA se correlacionó positivamente con CC (p=0,013), GLC (p=0,014), GLPP (p<0,001), TG y VLDL (p<0,001). CONCLUSIONES: El peor control glucémico se relaciona a mayores niveles de lípidos séricos y CC más elevada.<br>OBJECTIVE: To evaluate the relationship between anthropometric and biochemical variables in children and adolescents with type 1 diabetes mellitus (DM1). METHODS: This was a cross-sectional study of 11 children and 43 adolescents with DM1. The following data were collected: socioeconomic and demographic (age, sex, education, income), clinical (insulin therapy), anthropometric (weight, height, skinfolds, waist circumference - WC) and biochemical variables (glycated hemoglobin - HbA, casual blood glucose - CBG, post-prandial blood glucose - PPBG, and lipid profile). Statistical analysis included Student's t test (p<0.05) and Pearson's correlation (p<0.05). RESULTS: The average income per capita was 0.58±0.39 times the monthly minimum wage and 72.2% of the sample were on insulin therapy consisting of three doses per day. Most individuals had adequate height (92.6%) and BMI (87.0%) for their ages. Subjects with an adequate HbA index (inHbA) had lower CBG (p=0.002) and PPBG (p<0.001). There were positive correlations between inHbA and WC (p=0.013), CBG (p=0.014), PPBG (p<0.001), triglycerides and VLDL-cholesterol (p<0.001). CONCLUSIONS: Poorer glycemic control is related to higher serum lipids levels and larger WC

The number of X chromosomes influences protection from cardiac ischaemia/reperfusion injury in mice: one X is better than two

AIM: Sex differences in coronary heart disease have been attributed to sex hormones, whereas the potential role of the sex chromosomes has been ignored so far. Here, we investigated the role of the sex chromosomes in causing sex differences in myocardial ischaemia/reperfusion (I/R) injury. METHODS AND RESULTS: We used two unique mouse models, the ‘four core genotypes’ [XX mice with ovaries (XXF) or testes (XXM) and XY mice with ovaries (XYF) or testes (XYM)] and XY* (gonadal male or female mice with one or two X chromosomes). All mice were gonadectomized (GDX). In vivo or isolated Langendorff-perfused hearts were subjected to I/R injury. The in vivo infarct size in XY mice was significantly smaller than XX mice regardless of their gonadal type (24.5 ± 4.1% in XYF and 21.8 ± 3.3% in XYM vs. 37.0 ± 3.2% in XXF and 35.5 ± 2.1% in XXM, P < 0.01). Consistent with the results in vivo, the infarct size was markedly smaller and cardiac functional recovery was significantly better in XY mice compared with XX ex vivo. The mitochondrial calcium retention capacity was significantly higher in XY compared with XX mice (nmol/mg protein: XXF = 126 ± 9 and XXM = 192 ± 45 vs. XYF = 250 ± 56 and XYM = 286 ± 51, P < 0.05). In XY* mice, mice with 2X chromosomes had larger infarct size (2X females = 41.4 ± 8.9% and 2X males = 46.3 ± 9.5% vs. 1X females = 23.7 ± 3.9% and 1X males = 26.6 ± 6.9%, P < 0.05) and lower heart functional recovery, compared with those with 1X chromosome. Several X genes that escape X inactivation (Eif2s3x, Kdm6a, and Kdm5c) showed higher expression in XX than in XY hearts. CONCLUSION: XX mice have higher vulnerability to I/R injury compared with XY mice, which is due to the number of X chromosomes rather than the absence of the Y chromosome