PubMed · 14864826
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
C L ETHERIDGE, D E SANDO, E E FOLTZ. 1951. Dissecting aortic aneurysm.. https://pubmed.ncbi.nlm.nih.gov/14864826/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Claudin-14 (CLDN14) is a key component of tight junctions (TJs) critical for maintaining paracellular barrier function. Variants of CLDN14 have been linked to Vein of Galen malformations (VOGMs), a rare cerebrovascular disorder; however, the molecular mechanisms underlying their pathogenicity remain unknown. Here, we investigate the mechanistic effects of two VOGM-associated mutations, A113P and V143M, using reinforcement-learning driven enhanced sampling molecular dynamics simulations combined with DiffNets-based deep learning and independent trajectory-wide structural analyses. Our analysis reveals that A113P induces broader structural disruption of CLDN14, perturbing paracellular sealing, pore symmetry, and inter-protomer communication, whereas V143M induces structural rearrangements centred around TM3 and the TM3-ECL2 region. In both cases, mutation-specific alterations are observed in structural stability and interfacial organization across oligomeric assemblies. Notably, these effects are qualitatively consistent across different modelled architectures, despite variability in local responses. In the absence of experimentally resolved structures, the structural perturbations reported here provide a mechanistic understanding of how VOGM-associated variants may influence CLDN14 structure and dynamics.
OBJECTIVE: Endovascular treatment of intracranial wide-necked aneurysms employing stentgrafts might constitute a promising alternative to established neurosurgical or endovascular treatment options. However, there is uncertainity concerning long-term vessel patency and biocompatibility of the covering material used for these stentgrafts. The objective of our study was, therefore, to evaluate in an animal model of wide necked aneurysms, which changes within the parent vessel wall are present after stentgraft placement using polyurethane as the covering material. METHODS: Wide-necked aneurysms were created in rabbits by distal ligation and intraluminal incubation of the right common carotid artery with elastase. All 10 animals were treated with polyurethane covered stentgrafts. Angiography and histological analyses were performed including immunohistochemical investigations for estimating the proliferation of the intima and possible inflammatory infiltration of the vessel wall after one (n = 5) and three months (n = 5) observation. RESULTS: Stentgrafts led to a complete and stable aneurysm occlusion in all but one animal in which the stent was initially misplaced. In one animal, the stentgraft was completely occluded as visible both at angiography and on histological examination. Here, old thrombus was found within the stent although the animal was on antiplatelet therapy. The other stentgrafts remained patent and demonstrated only minimal proliferative carrier vessel wall changes and no in-stent stenosis. CONCLUSIONS: In previous animal models using Dacron covered stentgrafts, a poor short term patency rate due to the limited biocompatibility was found. We found, that Polyurethane seemed to have less adverse effects upon the vessel wall. However, a longer follow-up period is necessary to exclude delayed stenosis of the parent vessels. Stentgrafts may, therefore, play a role in broad based aneurysms, dissecting aneurysms or pseudoaneurysms, however, vessel sacrifice using permanent balloon occlusion may be a safer and better established alternative compared to the use of stentgrafts.
Explore the source record for details and available documents.