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A Geodesics-Based Surface Parameterization to Assess Aneurysm Progression.

ABSTRACT: Abdominal aortic aneurysm (AAA) intervention and surveillance is currently based on maximum transverse diameter, even though it is recognized that this might not be the best strategy. About 10% of patients with small AAA transverse diameters, for whom intervention is not considered, still rupture; while patients with large AAA transverse diameters, for whom intervention would have been recommended, have stable aneurysms that do not rupture. While maximum transverse diameter is easy to measure and track in clinical practice, one of its main drawbacks is that it does not represent the whole AAA and rupture seldom occurs in the region of maximum transverse diameter. By following maximum transverse diameter alone clinicians are missing information on the shape change dynamics of the AAA, and clues that could lead to better patient care. We propose here a method to register AAA surfaces that were obtained from the same patient at different time points. Our registration method could be used to track the local changes of the patient-specific AAA. To achieve registration, our procedure uses a consistent parameterization of the AAA surfaces followed by strain relaxation. The main assumption of our procedure is that growth of the AAA occurs in such a way that surface strains are smoothly distributed, while regions of small and large surface growth can be differentiated. The proposed methodology has the potential to unravel different patterns of AAA growth that could be used to stratify patient risks.

SUBMITTER: Phan L

PROVIDER: S-EPMC4843851 | biostudies-other | 2016 May

REPOSITORIES: biostudies-other

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A Geodesics-Based Surface Parameterization to Assess Aneurysm Progression.

Phan Ly L Courchaine Katherine K Azarbal Amir A Vorp David D Grimm Cindy C Rugonyi Sandra S

Journal of biomechanical engineering 20160501 5

Abdominal aortic aneurysm (AAA) intervention and surveillance is currently based on maximum transverse diameter, even though it is recognized that this might not be the best strategy. About 10% of patients with small AAA transverse diameters, for whom intervention is not considered, still rupture; while patients with large AAA transverse diameters, for whom intervention would have been recommended, have stable aneurysms that do not rupture. While maximum transverse diameter is easy to measure an ...[more]

PMID: 27003915

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Project description:The prediction of binding energies from the three-dimensional (3D) structure of a protein-ligand complex is an important goal of biophysics and structural biology. Here, we critically assess the use of empirical, solvent-accessible surface area-based calculations for the prediction of the binding of Src-SH2 domain with a series of tyrosyl phosphopeptides based on the high-affinity ligand from the hamster middle T antigen (hmT), where the residue in the pY+ 3 position has been changed. Two other peptides based on the C-terminal regulatory site of the Src protein and the platelet-derived growth factor receptor (PDGFR) are also investigated. Here, we take into account the effects of proton linkage on binding, and test five different surface area-based models that include different treatments for the contributions to conformational change and protein solvation. These differences relate to the treatment of conformational flexibility in the peptide ligand and the inclusion of proximal ordered solvent molecules in the surface area calculations. This allowed the calculation of a range of thermodynamic state functions (deltaCp, deltaS, deltaH, and deltaG) directly from structure. Comparison with the experimentally derived data shows little agreement for the interaction of SrcSH2 domain and the range of tyrosyl phosphopeptides. Furthermore, the adoption of the different models to treat conformational change and solvation has a dramatic effect on the calculated thermodynamic functions, making the predicted binding energies highly model dependent. While empirical, solvent-accessible surface area based calculations are becoming widely adopted to interpret thermodynamic data, this study highlights potential problems with application and interpretation of this type of approach. There is undoubtedly some agreement between predicted and experimentally determined thermodynamic parameters: however, the tolerance of this approach is not sufficient to make it ubiquitously applicable.

Project description:BACKGROUND:Long noncoding RNAs have emerged as critical molecular regulators in various biological processes and diseases. Here we sought to identify and functionally characterize long noncoding RNAs as potential mediators in abdominal aortic aneurysm development. METHODS:We profiled RNA transcript expression in 2 murine abdominal aortic aneurysm models, Angiotensin II (ANGII) infusion in apolipoprotein E-deficient ( ApoE-/-) mice (n=8) and porcine pancreatic elastase instillation in C57BL/6 wild-type mice (n=12). The long noncoding RNA H19 was identified as 1 of the most highly upregulated transcripts in both mouse aneurysm models compared with sham-operated controls. This was confirmed by quantitative reverse transcription-polymerase chain reaction and in situ hybridization. RESULTS:Experimental knock-down of H19, utilizing site-specific antisense oligonucleotides (LNA-GapmeRs) in vivo, significantly limited aneurysm growth in both models. Upregulated H19 correlated with smooth muscle cell (SMC) content and SMC apoptosis in progressing aneurysms. Importantly, a similar pattern could be observed in human abdominal aortic aneurysm tissue samples, and in a novel preclinical LDLR-/- (low-density lipoprotein receptor) Yucatan mini-pig aneurysm model. In vitro knock-down of H19 markedly decreased apoptotic rates of cultured human aortic SMCs, whereas overexpression of H19 had the opposite effect. Notably, H19-dependent apoptosis mechanisms in SMCs appeared to be independent of miR-675, which is embedded in the first exon of the H19 gene. A customized transcription factor array identified hypoxia-inducible factor 1? as the main downstream effector. Increased SMC apoptosis was associated with cytoplasmic interaction between H19 and hypoxia-inducible factor 1? and sequential p53 stabilization. Additionally, H19 induced transcription of hypoxia-inducible factor 1? via recruiting the transcription factor specificity protein 1 to the promoter region. CONCLUSIONS:The long noncoding RNA H19 is a novel regulator of SMC survival in abdominal aortic aneurysm development and progression. Inhibition of H19 expression might serve as a novel molecular therapeutic target for aortic aneurysm disease.

Dataset Information

A Geodesics-Based Surface Parameterization to Assess Aneurysm Progression.

Publications

A Geodesics-Based Surface Parameterization to Assess Aneurysm Progression.

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