The Association Between Curvature and Rupture in a Murine Model of Abdominal Aortic Aneurysm and Dissection.

BACKGROUND: Mouse models of abdominal aortic aneurysm (AAA) and dissection have proven to be invaluable in the advancement of diagnostics and therapeutics by providing a platform to decipher response variables that are elusive in human populations. One such model involves systemic Angiotensin II (Ang-II) infusion into low density-lipoprotein receptor-deficient (LDLr-/-) mice leading to intramural thrombus formation, inflammation, matrix degradation, dilation, and dissection. Despite its effectiveness, considerable experimental variability has been observed in AAAs taken from our Ang-II infused LDLr-/- mice (n=12) with obvious dissection occurring in 3 samples, outer bulge radii ranging from 0.73 to 2.12 mm, burst pressures ranging from 155 to 540 mmHg, and rupture location occurring 0.05 to 2.53 mm from the peak bulge location. OBJECTIVE: We hypothesized that surface curvature, a fundamental measure of shape, could serve as a useful predictor of AAA failure at supra-physiological inflation pressures. METHODS: To test this hypothesis, we fit well-known biquadratic surface patches to 360° micro-mechanical test data and used Spearman's rank correlation (rho) to identify relationships between failure metrics and curvature indices. RESULTS: We found the strongest associations between burst pressure and the maximum value of the first principal curvature (rho=-0.591, p-val=0.061), the maximum value of Mean curvature (rho=-0.545, p-val=0.087), and local values of Mean curvature at the burst location (rho=-0.864, p-val=0.001) with only the latter significant after Bonferroni correction. Additionally, the surface profile at failure was predominantly convex and hyperbolic (saddle-shaped) as indicated by a negative sign in the Gaussian curvature. Findings reiterate the importance of shape in experimental models of AAA.

Obstacles to translating the promise of nanoparticles into viable amyloid disease therapeutics.

Nanoparticles (NPs) constitute a powerful therapeutic platform with exciting prospects as potential inhibitors of amyloid-[Formula: see text] (Aß) aggregation, a process associated with Alzheimer's disease (AD). Researchers have synthesized and tested a large collection of NPs with disparate sizes, shapes, electrostatic properties and surface ligands that evoke a variety of responses on Aß aggregation. In spite of a decade of research on the NP-Aß system and many promising experimental results, NPs have failed to progress to any level of clinical trials for AD. A theoretical framework with which to approach this physical system is presented featuring two simple metrics, (1) the extent to which NPs adsorb Aß, and (2) the degree to which interaction with a NP alters Aß conformation relative to aggregation propensity. Most of our current understanding of these two interactions has been gained through experimentation, and many of these studies are reviewed herein. We also provide a potential roadmap for studies that we believe could produce viable NPs as an effective AD therapeutic platform.