RESUMEN
Aortic aneurysms, life-threatening and often undetected until they cause sudden death, occur when the aorta dilates beyond 1.5 times its normal size. This study used ultrasound scans and micro-computed tomography to monitor and measure aortic volume in preclinical settings, comparing it to the well-established measurement using ultrasound scans. The reproducibility of measurements was also examined for intra- and inter-observer variability, with both modalities used on 8-week-old C57BL6 mice. For inter-observer variability, the µCT (micro-computed tomography) measurements for the thoracic, abdominal, and whole aorta between observers were highly consistent, showing a strong positive correlation (R2 = 0.80, 0.80, 0.95, respectively) and no significant variability (p-value: 0.03, 0.03, 0.004, respectively). The intra-observer variability for thoracic, abdominal, and whole aorta scans demonstrated a significant positive correlation (R2 = 0.99, 0.96, 0.87, respectively) and low variability (p-values = 0.0004, 0.002, 0.01, respectively). The comparison between µCT and USS (ultrasound) in the suprarenal and infrarenal aorta showed no significant difference (p-value = 0.20 and 0.21, respectively). µCT provided significantly higher aortic volume measurements compared to USS. The reproducibility of USS and µCT measurements was consistent, showing minimal variance among observers. These findings suggest that µCT is a reliable alternative for comprehensive aortic phenotyping, consistent with clinical findings in human data.
RESUMEN
OBJECTIVE: The aim of this study was to investigate the reproducibility of anterior-posterior diameter (APdmax) and three-dimensional lumen volume (3DLV) measurements of abdominal aortic aneurysms (AAA) in a classical murine AAA model. We also compared the magnitude of change in the aortic size detected with each method of assessment. METHODS: Periadventitial application of porcine pancreatic elastase (PPE AAA) or sham surgery was performed in two cohorts of mice. Cohort 1 was used to assess for observer variability with the APdmax and 3DLV measurements. Cohort 2 highlighted the relationship between APdmax and 3DLV and changes in AAA detected. RESULTS: There was no significant observer variability detected with APdmax measurement. Similarly, no significant intraobserver variability was evident with 3DLV; however, a small but significant interobserver difference was present. APdmax and 3DLV measurements of PPE AAA significantly correlated. However, changes in the AAA morphology were detected earlier with 3DLV. CONCLUSION: APdmax and 3DLV are both reliable methods for measuring an AAA. Both these methods correlate with each other. However, changes in AAA morphology were detected earlier with 3DLV, which is important to detect subtle but important changes to aortic geometry in a laboratory setting. 3DLV measurement of AAA is a simple, reproducible, and comprehensive method for assessing changes in disease morphology.
RESUMEN
Insulin resistance is characterized by excessive endothelial cell generation of potentially cytotoxic concentrations of reactive oxygen species. We examined the role of NADPH oxidase (Nox) and specifically Nox2 isoform in superoxide generation in two complementary in vivo models of human insulin resistance (endothelial specific and whole body). Using three complementary methods to measure superoxide, we demonstrated higher levels of superoxide in insulin-resistant endothelial cells, which could be pharmacologically inhibited both acutely and chronically, using the Nox inhibitor gp91ds-tat. Similarly, insulin resistance-induced impairment of endothelial-mediated vasorelaxation could also be reversed using gp91ds-tat. siRNA-mediated knockdown of Nox2, which was specifically elevated in insulin-resistant endothelial cells, significantly reduced superoxide levels. Double transgenic mice with endothelial-specific insulin resistance and deletion of Nox2 showed reduced superoxide production and improved vascular function. This study identifies Nox2 as the central molecule in insulin resistance-mediated oxidative stress and vascular dysfunction. It also establishes pharmacological inhibition of Nox2 as a novel therapeutic target in insulin resistance-related vascular disease.