Elevated serum neutrophil elastase is related to prehypertension and airflow limitation in obese women

<p>Abstract</p> <p>Background</p> <p>Neutrophil elastase level/activity is elevated in a variety of diseases such as atherosclerosis, systolic hypertension and obstructive pulmonary disease. It is unknown whether obese individuals with prehypertension also have elevated neutrophil elastase, and if so, whether it has a deleterious effect on pulmonary function. Objectives: To determine neutrophil elastase levels in obese prehypertensive women and investigate correlations with pulmonary function tests.</p> <p>Methods</p> <p>Thirty obese prehypertensive women were compared with 30 obese normotensive subjects and 30 healthy controls. The study groups were matched for age. Measurements: The following were determined: body mass index, waist circumference, blood pressure, lipid profile, high sensitivity C-reactive protein, serum neutrophil elastase, and pulmonary function tests including forced expiratory volume in one second (FEV₁), forced vital capacity (FVC) and FEV₁/FVC ratio.</p> <p>Results</p> <p>Serum neutrophil elastase concentration was significantly higher in both prehypertensive (405.8 ± 111.6 ng/ml) and normotensive (336.5 ± 81.5 ng/ml) obese women than in control non-obese women (243.9 ± 23.9 ng/ml); the level was significantly higher in the prehypertensive than the normotensive obese women. FEV1, FVC and FEV1/FVC ratio in both prehypertensive and normotensive obese women were significantly lower than in normal controls, but there was no statistically significant difference between the prehypertensive and normotensive obese women. In prehypertensive obese women, there were significant positive correlations between neutrophil elastase and body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, low density lipoprotein cholesterol, high sensitivity C-reactive protein and negative correlations with high density lipoprotein cholesterol, FEV1, FVC and FEV1/FVC.</p> <p>Conclusion</p> <p>Neutrophil elastase concentration is elevated in obese prehypertensive women along with an increase in high sensitivity C-reactive protein which may account for dyslipidemia and airflow dysfunction in the present study population.</p

Arterial stiffening in western diet-fed mice is associated with increased vascular elastin, transforming growth factor-ß, and plasma neuraminidase

Consumption of excess fat and carbohydrate (Western diet, WD) is associated with alterations in the structural characteristics of blood vessels. This vascular remodeling contributes to the development of cardiovascular disease, particularly as it affects conduit and resistance arteries. Vascular remodeling is often associated with changes in the elastin-rich internal elastic lamina (IEL) and the activation of transforming growth factor (TGF)-ß. In addition, obesity and type II diabetes have been associated with increased serum neuraminidase, an enzyme known to increase TGF-ß cellular output. Therefore, we hypothesized that WD-feeding would induce structural modifications to the IEL of mesenteric resistance arteries in mice, and that these changes would be associated with increased levels of circulating neuraminidase and the up-regulation of elastin and TGF-ß in the arterial wall. To test this hypothesis, a WD, high in fat and sugar, was used to induce obesity in mice, and the effect of this diet on the structure of mesenteric resistance arteries was investigated. 4-week old, Post-weaning mice were fed either a normal diet (ND) or WD for 16 weeks. Mechanically, arteries from WD-fed mice were stiffer and less distensible, with marginally increased wall stress for a given strain, and a significantly increased Young's modulus of elasticity. Structurally, the wall cross-sectional area and the number of fenestrae found in the internal elastic lamina (IEL) of mesenteric arteries from mice fed a WD were significantly smaller than those of arteries from the ND-fed mice. There was also a significant increase in the volume of elastin, but not collagen in arteries from the WD cohort. Plasma levels of neuraminidase and the amount of TGF-ß in mesenteric arteries were elevated in mice fed a WD, while ex vivo, cultured vascular smooth muscle cells exposed to neuraminidase secreted greater amounts of tropoelastin and TGF-ß than those exposed to vehicle. These data suggest that consumption of a diet high in fat and sugar causes stiffening of the vascular wall in resistance arteries through a process that may involve increased neuraminidase and TGF-ß activity, elevated production of elastin, and a reduction in the size and number of fenestrae in the arterial IEL

Elastin-Derived Peptides Are New Regulators of Insulin Resistance Development in Mice

Although it has long been established that the extracellular matrix acts as a mechanical support, its degradation products, which mainly accumulate during aging, have also been demonstrated to play an important role in cell physiology and the development of cardiovascular and metabolic diseases. In the current study, we show that elastin-derived peptides (EDPs) may be involved in the development of insulin resistance (IRES) in mice. In chow-fed mice, acute or chronic intravenous injections of EDPs induced hyperglycemic effects associated with glucose uptake reduction and IRES in skeletal muscle, liver, and adipose tissue. Based on in vivo, in vitro, and in silico approaches, we propose that this IRES is due to interaction between the insulin receptor (IR) and the neuraminidase-1 subunit of the elastin receptor complex triggered by EDPs. This interplay was correlated with decreased sialic acid levels on the β-chain of the IR and reduction of IR signaling. In conclusion, this is the first study to demonstrate that EDPs, which mainly accumulate with aging, may be involved in the insidious development of IRES

EFFECT OF AGE ON THE BIOMECHANICAL AND MICROCIRCULATORY PROPERTIES OF THE SKIN IN HEALTHY INDIVIDUALS AND DURING VENOUS ULCERATION

Background: With aging there is alteration of elastic properties of the skin and skin-blood flow. Aim: The purpose of this study was to compare age-related changes in selected biomechanical parameters of the skin (skin hardness, skin extensibility, relaxation time constant, τ) and subcutaneous microcirculatory quality (SMQ) in individuals with and without venous diseases. Materials and Methods: Two groups were studied: the first group was of asymptomatic healthy individuals and the second group included patients with chronic venous insufficiency (CVI) and venous ulceration, without edema. Both groups were subdivided to three age categories (21-40, 41-60 and 61-90 years old). Skin hardness was measured by durometer, extensibility and τ were measured using extensometer and SQM was assessed via postural vasoconstrictive response (LDF). Results: Results showed that skin hardness, extensibility, and τ-values were increased, whereas LDF was decreased in the older groups as compared with younger groups. These changes are attributed to alterations in the skin structure and reduced capillaries density networks. Similar behavior was found in the biomechanical and microcirculatory changes in patients with venous ulceration and CVI, but these changes were more increased further in older patients with venous ulceration as compared with older patients with CVI and that can be attribute to more intense response against tissue injury. Conclusions: Since aging elevated skin hardness and extensibility, but lowered vasoconstrictive response in individuals, with and without, venous diseases, we conclude that aging process is likely to cause an accumulation of damaged skin tissues and that could induce an apparent antigen-driven response that altered skin structure and the subsequent biomechanical properties obtained in this study