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Foster, E. P.

Publications and source records attributed to Foster, E. P..

2 recordsLinked to original sources
bioRxiv2025

Murine Abdominal Aortic Aneurysm Intraluminal Thrombus Composition and Structure

An abdominal aortic aneurysm (AAA) is a dilation of the aortic wall in the abdomen. Many AAA patients develop intraluminal thrombus (ILT), but the role of ILT in AAA progression and rupture is not well understood. To evaluate ILT in AAAs, we induced AAAs in male C57Bl6/J mice (n=25) via surgical application of topical elastase (5 {micro}L of 5 or 10 mg/mL) to the abdominal aorta below the renal arteries and administration of {beta}-aminopropionitrile (BAPN, 0.2%) drinking water. We collected weekly/biweekly ultrasound images over 56 days. Mice were euthanized and histology images were collected. We semi-quantitatively assessed elastin degradation and inflammation from Movats pentachrome and H&E-stained samples, respectively. Mice with ILT had more significant expansion over the length of the study (beginning at day 14, p<0.05). From histology, ILT samples showed more elastin disorganization and greater inflammation. From scanning electron microscopy, we were able to confirm the presence of layered sheets of fibrin and abnormally shaped red blood cells (polyhedrocytes) within the ILT deposits. In this model, elastase causes aortic injury by degrading elastin fibrils in the aortic wall, reducing the ability of the aorta to contract during high-pressure blood flow. Further damage to the extracellular matrix is likely driven by subsequent inflammation. Here we observed tissue samples with greater acute-on-chronic inflammation were correlated with more elastin damage, and therefore greater aortic expansion. Further, larger aortic expansions were correlated with slower blood flow, likely due to increased cross-sectional area. Thus, increased aortic expansion and damage to the aortic wall may be more likely to create hemodynamic conditions that are conducive to the initiation of ILT deposition: endothelial damage and reduced blood flow. Understanding the relationship between ILT formation, aortic wall degradation, and inflammation could help refine therapeutic strategies for treating AAAs. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/685150v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@f6ba71org.highwire.dtl.DTLVardef@4a8379org.highwire.dtl.DTLVardef@1fd97c1org.highwire.dtl.DTLVardef@1f60400_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗
bioRxiv2021

Nanocrown electrodes for robust and scalable intracellular recordings of cardiomyocytes for cardiotoxicity screening

Drug-induced cardiotoxicity arises primarily when a compound alters the electrophysiological properties of cardiomyocytes. Features of intracellular action potentials (iAPs) are powerful biomarkers that predict proarrhythmic risks. However, the conventional patch clamp techniques for measuring iAPs are either laborious and low throughput or not suitable for measuring electrically connected cardiomyocytes. In the last decade, a number of vertical nanoelectrodes have been demonstrated to achieve parallel and minimally-invasive iAP recordings. Nanoelectrodes show great promise, but the large variability in success rate, signal strength, and the low throughput of device fabrication have hindered them from being broadly adopted for proarrhythmia drug assessment. In this work, we developed vertically-aligned and semi-hollow nanocrown electrodes that are mechanically robust and made through a scalable fabrication process. Nanocrown electrodes achieve >99% success rates in obtaining intracellular access through electroporation, allowing reliable and simultaneous iAP recordings from up to 57 human pluripotent stem-cell-derived cardiomyocytes (hPSC-CMs). The accuracy of nanocrown electrode recordings is validated by simultaneous patch clamp recording from the same cell. Nanocrown electrodes enable prolonged iAP recording for continual monitoring of the same cells upon the sequential addition of four to five incremental drug doses. In this way, the dose-response data is self-referencing, which avoids the cell-to-cell variations inherent to hPSC-CMs. We are hopeful that this technology development is a step towards establishing an iAP screening assay for preclinical evaluation of drug-induced arrhythmogenicity.

bioengineering↗