Flow mediated dilatation over the natural history of abdominal aortic aneurysms

<p>Abdominal aortic aneurysm, an abnormal dilatation of the descending aorta, disproportionately affects males and is often asymptomatic until rupture, posing major risk of mortality. The natural history varies greatly in individuals; some patients remain at subclinical aortic diameters for decades, others rapidly progress to sizes indicating surgical intervention. Surgical mortality is associated with age, so it is advantageous to predict growth of AAA. The biochemical implications of wall degradation may have systemic inflammatory effects which adversely affect the endothelium, which regulates vasomotor tone. Vasodilation is modulated by the release of nitric oxide and the measurement of flow mediated dilatation (FMD) is a widely used proxy for NO bioavailability. The goal of this study is to examine changes of FMD over time and its predictive value in AAA growth. We hypothesise that FMD correlates with future growth rate of AAAs in humans.</p> <p>In FMD, ultrasonography is used to measure the diameter of an artery before and after it is subjected to shear stress through temporary limb ischaemia. No past study of AAA patients has examined serial measurements of FMD. The OxAAA study collects serial measurements on AAA patients under surveillance and undergoing surgery. FMD predicts future aneurysm growth of AAA patients and FMD deteriorates over time. Due to its non-invasive and cost effective nature, FMD is useful in predicting the growth of AAA, and has also been shown to predict cardiovascular events, serving a two-fold purpose. In clinical contexts, it may be used to foresee imminent need for AAA repair, allowing for pre-surgical lifestyle changes. FMD may also indicate future growth, allowing for less frequent surveillance and reducing costs.</p

Additional file 4: of What are the non-food impacts of GM crop cultivation on farmers’ health?

Table S3. All articles published on the studies analysed

Impact of acute stressor and adrenergic regulation of plasma exosomes miRNA.

<p>Exposure to tail shock stress (Stress) significantly reduced plasma exosome miR-142-52 and -203. Intraperitoneal administration of the α₁-ADR antagonist prazosin (2.0 mg/kg) 30 min prior to Stress attenuated the stress-induced down-regulation of miR-142-5p, but not miR-203. *indicates significant fold change when compared to plasma exosomes from control rats in the absence of prazosin (p<0.05). #indicates significant effect of prazosin (p<0.05). Two-way ANOVA with Fisher PLSD post hoc test was used.</p

Exposure to an acute stressor modifies the proteomic profile of circulating plasma exosomes.

<p>A. Male Fisher 344 rats exposed to inescapable tail shocks (Stress) had elevated plasma concentrations of Hsp72 compared to non-stressed rats (Control). Following exosome enrichment with ExoQuick precipitation, B. concentrations of Hsp72 were the highest in the exosome enriched fractions from stressed rats. C. Correction with CD63 particles confirmed that exposure to stress increases Hsp72 concentrations in the exosome enriched fraction compared to control conditions. D. Lysing the exosome enriched fraction increased Hsp72 concentrations for both the stress and control groups, but the impact of stressor exposure was restricted to the not lysed group. E. Following pre-treatment with Thromboplastin-D, plasma was divided and either treated with magnetic Dynabeads coated in CD63 antibodies (Anti-CD63) to immunoprecipitate CD63 particles from the plasma or left undisturbed (No Treatment) prior to ExoQuick precipitation. Anti-CD63 treatment attenuates CD63 concentrations in the plasma exosome enriched fractions from stressed rats compared no treatment conditions. F. Anti-CD63 treatment also attenuates Hsp72 in the plasma exosome enriched fractions from stressed rats compared to no treatment conditions. Results are expressed in means ± SE; 6–8 rats/condition. *indicates significant difference when compared to control rats (p<0.05). #indicates significant difference when compared to exosome depleted fraction (p<0.05). Two-way ANOVA with Fisher PLSD post hoc test was used.</p

Confirmation of successful plasma exosome enrichment from male Fisher 344 rats.

<p>A. TEM demonstrates successful isolation of exosome-sized particles (∼80 nm) from the plasma with ExoQuick precipitation. B. TEM shows how pre-treating plasma with Thromboplastin-D prior to exosome isolation with ExoQuick removes clouding factors and prevents vesicle aggregation. C. Exosome enriched and exosome depleted plasma fractions from stressed rats pre-treated with Thromboplastin-D were characterized for size distribution and quantitated by NanoSight LM10, using light scatter from a 532 nm green laser. ELISA analyses reveal that ExoQuick exosome isolation successfully enriches exosomes as marked by known exosome markers. Exposing rats to tail shock stress (Stress) had no impact on the rate of plasma exosome release compared to non-stressed rats (Control) as measured by: D. the tetraspanin CD63, E. the adhesion molecule Rab5b, F. and the intestinal exosome marker A33. G. Analysis of IL-6 confirms activation of the stress response and specificity of ExoQuick for exosome associated proteins. These data suggest that stress does not impact the rate of exosome release into the plasma. Proteomic results are expressed in means ± SE; 6–8 rats/condition. *indicates significant difference when compared to control rats (p<0.05). #indicates significant difference when compared to exosome depleted fraction (p<0.05). Two-way ANOVA with Fisher PLSD post hoc test was used.</p

Functionally enriched pathways impacted by miR-142-5p and miR-203.

<p>KEGG and Wikipathway (Wiki) analysis revealed functionally enriched pathway categories generated from genes significantly differentially represented in plasma exosomes from rats exposed to inescapable tail shock.</p><p>Functionally enriched pathways impacted by miR-142-5p and miR-203.</p

Adrenergic regulation of exosomal Hsp72.

<p>Adult male Fisher 344 rats were either injected intraperitoneally with the α₁-ADR antagonist prazosin (2.0 mg/kg) 30 min prior to exposure to tail shock stress (Stress) or left undisturbed. Plasma analysis reveals that prazosin administration A. significantly attenuates stress-induced elevations of Hsp72 as well as B. lactate dehydrogenase activity, a marker of cell death. Exosomes were fractionated with ExoQuick in the stressed rats, revealing that prazosin administration C. had no effect on CD63 particle concentrations, but D. significantly attenuates Hsp72 concentration in both the exosome depleted and exosome enriched fractions. Results are expressed in means ± SE; 6–8 rats/condition. *indicates significant difference when compared to control rats (p<0.05). #indicates significant difference when compared to no treatment group or exosome depleted fraction (p<0.05). Two-way ANOVA with Fisher PLSD post hoc test was used.</p

Results of logistic regression analysis conducted in five countries: relative odds of two health outcomes associated with (1) physical fighting and (2) weapon carrying, 2006 <i>(Boys)</i>^*.

*<p>(1) Models simultaneously adjusted for age, socio-economic status, physical activity, smoking, drinking, evenings out with friends, and bullying victimization.</p

Prevalence of physical fighting, weapon carrying, and potential adolescent health outcomes, percentages (standard errors) by gender and country, 2006.

<p>Prevalence of physical fighting, weapon carrying, and potential adolescent health outcomes, percentages (standard errors) by gender and country, 2006.</p

Demographic characteristics of study samples in five HBSC countries, 2006.

<p>Demographic characteristics of study samples in five HBSC countries, 2006.</p