Genetically engineered resistance for MMP collagenases promotes abdominal aortic aneurysm formation in mice infused with angiotensin II.

Clinical evidence links increased aortic collagen content and stiffness to abdominal aortic aneurysm (AAA) formation. However, the possibility that excess collagen contributes to AAA formation remains untested. We investigated the hypothesis that augmented collagen promotes AAA formation, and employed apoE-null mice expressing collagenase-resistant mutant collagen (Col(R/R)/apoE(-/-)), heterozygote (Col(R/+)/apoE(-/-)), or wild-type collagen (Col(+/+)/apoE(-/-)) infused with angiotensin II to induce AAA.

Time-Saving Benefits of Intravital Staining.

One of the challenges in labeling tissues for fluorescence microscopy is minimizing sample processing while maintaining or improving the information generated by the fluorescent label. Generally, tissues are extracted, fixed, and embedded in mounting media (such as paraffin), sectioned, and then postprocessed by removing the paraffin, blocking, labeling, and washing. Despite all of these steps, the consistency of labeling quality can vary as a result of several factors, including heterogeneity in labeling efficiency from slide to slide, the necessity of postprocessing to obtain information on sequential sections of tissue, interference from the mounting media, and loss of native three-dimensional structural information, especially in thicker sections.

High-resolution whole organ imaging using two-photon tissue cytometry.

Three-dimensional (3-D) tissue imaging offers substantial benefits to a wide range of biomedical investigations from cardiovascular biology, diabetes, Alzheimer's disease to cancer. Two-photon tissue cytometry is a novel technique based on high-speed multiphoton microscopy coupled with automated histological sectioning, which can quantify tissue morphology and physiology throughout entire organs with subcellular resolution. Furthermore, two-photon tissue cytometry offers all the benefits of fluorescence-based approaches including high specificity and sensitivity and appropriateness for molecular imaging of gene and protein expression.

Oxidative stress and thioredoxin-interacting protein promote intravasation of melanoma cells.

Although intravasation may be a critical rate-limiting step in the metastatic cascade, the role of oxidative stress in intravasation is unknown. We tested the hypothesis that reactive oxygen species (ROS), regulated by thioredoxin interacting protein (Txnip) through the action of thioredoxin (Trx), influence human SK-MEL-28 melanoma cell reverse (basolateral-to-apical) transendothelial migration (TEM) in vitro as a model for intravasation. Reverse transendothelial migration was dose-dependently induced by hydrogen peroxide 2.

Cell stiffness and receptors: evidence for cytoskeletal subnetworks.

Viscoelastic models of cells often treat cells as homogeneous objects. However, studies have demonstrated that cellular properties are local and can change dramatically on the basis of the location probed. Because membrane receptors are linked in various ways to the intracellular space, with some receptors linking to the cytoskeleton and others diffusing freely without apparent linkages, the cellular physical response to mechanical stresses is expected to depend on the receptor engaged.

Thioredoxin-interacting protein controls cardiac hypertrophy through regulation of thioredoxin activity.

Background: Although cellular redox balance plays an important role in mechanically induced cardiac hypertrophy, the mechanisms of regulation are incompletely defined. Because thioredoxin is a major intracellular antioxidant and can also regulate redox-dependent transcription, we explored the role of thioredoxin activity in mechanically overloaded cardiomyocytes in vitro and in vivo.

Methods And Results: Overexpression of thioredoxin induced protein synthesis in cardiomyocytes (127+/-5% of controls, P<0.