Lung exposure to lipopolysaccharide causes atherosclerotic plaque destabilisation.

Epidemiological studies have implicated lung inflammation as a risk factor for acute cardiovascular events, but the underlying mechanisms linking lung injury with cardiovascular events are largely unknown.Our objective was to develop a novel murine model of acute atheromatous plaque rupture related to lung inflammation and to investigate the role of neutrophils in this process.Lipopolysaccharide (LPS; 3 mg·kg(-1)) or saline (control) was instilled directly into the lungs of male apolipoprotein E-null C57BL/6J mice following 8 weeks of a Western-type diet. 24 h later, atheromas in the right brachiocephalic trunk were assessed for stability ex vivo using high-resolution optical projection tomography and histology. 68% of LPS-exposed mice developed vulnerable plaques, characterised by intraplaque haemorrhage and thrombus, versus 12% of saline-exposed mice (p=0.0004). Plaque instability was detectable as early as 8 h post-intratracheal LPS instillation, but not with intraperitoneal instillation. Depletion of circulating neutrophils attenuated plaque rupture.We have established a novel plaque rupture model related to lung injury induced by intratracheal exposure to LPS. In this model, neutrophils play an important role in both lung inflammation and plaque rupture. This model could be useful for screening therapeutic targets to prevent acute vascular events related to lung inflammation.

Pappa2 deletion has sex- and age-specific effects on bone in mice.

OBJECTIVE: In humans, loss-of-function mutations in the gene encoding pregnancy-associated pregnancy protein-A2 cause short stature and slightly reduced bone density. The goal of this study was to determine the effects of Pappa2 deletion on bone in mice. DESIGN: Pappa2 deletion mice and littermate controls were culled at 10, 19 or 30 weeks of age and femurs were analysed by micro-computed tomography. Serum markers of bone turnover and insulin-like growth factor binding protein 5 (IGFBP-5), a proteolytic target of PAPP-A2, were measured by ELISA. RESULTS: At 10 and 19 weeks of age, Pappa2 deletion mice had slightly reduced trabecular parameters, but by 19 weeks of age, female deletion mice had increased cortical tissue mineral density, and this trait was increased by a small amount in deletion mice of both sexes at 30 weeks. Cortical area fraction was increased in Pappa2 deletion mice at all ages. Deletion of Pappa2 increased circulating IGFBP-5 levels and reduced markers of bone turnover (PINP and TRACP 5b). CONCLUSIONS: PAPP-A2 contributes to the regulation of bone structure and mass in mice, likely through control of IGFBP-5 levels. The net effect of changes in bone formation and resorption depend on sex and age, and differ between trabecular and cortical bone.

Mechanical stimuli of trabecular bone in osteoporosis: A numerical simulation by finite element analysis of microarchitecture.

Mechanical stimuli are one of the factors that influence bone cell activity and therefore the remodeling of bone. These stimuli are dependent on the microarchitecture of the tissue and can be altered by changes in the bone that occur typically with osteoporosis. The objective of this study was to quantify the variation in the mechanical stimuli of trabecular bone due to changes in the microarchitecture. The morphology of 76 cubes of trabecular bone from human tibia were obtained from microcomputed tomography images and estimated possibilities for mechanical stimuli were determined using poro-viscoelastic finite element models based on the three-dimensional images. The distributions of Von Mises stress, octahedral strain, strain energy density, fluid velocity and pore pressure were predicted for the solid and the marrow phases of bone. We predicted that with variations in the morphology of the trabecular bone, such as an increase of 30% porosity, there is a significant decrease in the mechanical stimuli of the tissue when subjected to constant strain. The average stress and strain in the bone phase may reduce 50% and the fluid velocity in the marrow phase 88%. These decreases may intrinsically affect the mechanoregulation of bone regeneration that contributes to the etiology of osteoporosis.

Competitive trampolining influences trabecular bone structure, bone size, and bone strength.

BACKGROUND: Trampolining is a form of gymnastics that has increased in popularity over the last decade and due to its concurrence with the formative years of bone development, it may have an important impact on bone health. However, bone density, microarchitecture, and bone strength of competitive trampolinists have not been explored. Therefore, the purpose of this cross-sectional study was to investigate the relationship between trampolining participation and (1) bone density, area, and microarchitecture; and (2) estimated bone strength and the role of muscle and impact loading in young female adults. METHODS: We recruited 29 female participants aged 16-29 years for this study (n = 14 trampolinists; n = 15 controls). Skeletal parameters were assessed using dual X-ray absorptiometry, high-resolution peripheral quantitative computed tomography (HR-pQCT), and finite element analysis (FEA). Muscle strength was measured using dynamometers. RESULTS: Trampolinists had higher bone density at the hip and spine, greater trabecular density and thicker trabeculae at the tibia, as well as larger bones at both the tibia and radius than controls (p < 0.05). Trampolinists also had higher muscle strength than controls at the lower body with no difference between groups in the upper body. Estimates of bone strength using FEA were greater for trampolinists than controls at both the radius and tibia. CONCLUSION: This is the first study to investigate bone density, area, and microarchitecture in female trampolinists using HR-pQCT. Trampolinists had greater bone density, area, microarchitecture, and estimated bone strength than controls.

The poro-viscoelastic properties of trabecular bone: a micro computed tomography-based finite element study.

Bone is a porous structure with a solid phase that contains hydroxyapatite and collagen. Due to its composition, bone is often represented either as a poroelastic or as a viscoelastic material; however, the poro-viscoelastic formulation that allows integrating the effect of both the fluid flow and the collagen on the mechanical response of the tissue, has not been applied yet. The objective of this study was to develop a micro computed tomography (µCT)-based finite element (FE) model of trabecular bone that includes both the poroelastic and the viscoelastic nature of the tissue. Cubes of trabecular bone (N=25) from human distal tibia were scanned with µCT and stress relaxation experiments were conducted. The µCT images were the basis for sample specific FE models, and the stress relaxation experiments were simulated applying a poro-viscoelastic formulation. The model considers two scales of the tissue: the intertrabecular pore and the lacunar-canalicular pore scales. Independent viscoelastic and poroelastic models were also developed to determine their contribution to the poro-viscoelastic model. All the experiments exhibited a similar relaxation trend. The average reaction force before relaxation was 9.28 × 10(2)N (SD ± 5.11 × 10(2)N), and after relaxation was 4.69 × 10(2)N (SD ± 2.88 × 10(2)N). The slope of the regression line between the force before and after relaxation was 1.92 (R(2)=0.96). The poro-viscoelastic models captured 49% of the variability of the experimental data before relaxation and 33% after relaxation. The relaxation predicted with viscoelastic models was similar to the poro-viscoelastic ones; however, the poroelastic formulation underestimated the reaction force before relaxation. These data suggest that the contribution of viscoelasticity (fluid flow-independent mechanism) to the mechanical response of the tissue is significantly greater than the contribution of the poroelasticity (fluid flow-dependent mechanism).