Evaluation of the effects of glucose and oxygen on the vascular endothelial cell migration.

Glucose is essential as the main energy source for living organisms. However, excessive elevation of blood sugar levels can lead to diabetes and serious complications such as arteriosclerosis. Even though blood sugar levels as well as hypoxia associated with hyperglycemia are known to be closely related to diabetes complications, the responses of vascular endothelial cells to glucose and oxygen have not been fully investigated. In this study, using a microfluidic device that can control the oxygen concentration, we observed the behavior of vascular endothelial cell monolayers while simultaneously controlling glucose and oxygen levels. Results showed that the cell migration speed was increased by high-glucose exposure in an oxygen-rich environment, but was decreased in a hypoxic environment regardless of glucose condition. The expression of vascular endothelial-cadherin at the cell periphery, which plays a role in cell-cell adhesion, was increased by hypoxic exposure, but was largely independent of glucose condition. This suggested that cell-cell adhesion is less involved in the increase in migration caused by high glucose. Furthermore, stabilization and nuclear translocation of hypoxia-inducible factor-1α, which is involved in cellular hypoxia sensing, increased 5 h after exposure to high glucose, but decreased 3 days after the exposure. This indicated that intracellular hypoxia was generated by increased oxygen consumption in mitochondria just after the high-glucose exposure, but it was moderated within 3 days.

Mechanical regulation of bone homeostasis through p130Cas-mediated alleviation of NF-κB activity.

Mechanical loading plays an important role in bone homeostasis. However, molecular mechanisms behind the mechanical regulation of bone homeostasis are poorly understood. We previously reported p130Cas (Cas) as a key molecule in cellular mechanosensing at focal adhesions. Here, we demonstrate that Cas is distributed in the nucleus and supports mechanical loading-mediated bone homeostasis by alleviating NF-κB activity, which would otherwise prompt inflammatory processes. Mechanical unloading modulates Cas distribution and NF-κB activity in osteocytes, the mechanosensory cells in bones. Cas deficiency in osteocytes increases osteoclastic bone resorption associated with NF-κB-mediated RANKL expression, leading to osteopenia. Upon shear stress application on cultured osteocytes, Cas translocates into the nucleus and down-regulates NF-κB activity. Collectively, fluid shear stress-dependent Cas-mediated alleviation of NF-κB activity supports bone homeostasis. Given the ubiquitous expression of Cas and NF-κB together with systemic distribution of interstitial fluid, the Cas-NF-κB interplay may also underpin regulatory mechanisms in other tissues and organs.

Estimation of force on vascular wall caused by insertion of self-expanding stents.

Stent placement is a minimally invasive procedure that has received considerable attention as a treatment option for vascular stenotic lesions associated with coronary atherosclerosis. However, the severe problem of in-stent restenosis has recently begun to occur in blood vessels in which long-term placement of stents has occurred. In-stent restenosis results from the increase in neointimal hyperplasia caused by the stimulus of the force on the vascular wall. In the present study, methods are proposed to compute the contact force and straightening force on a vascular wall. The force on the vascular wall is calculated using these methods. As an example, the force on the vascular wall created by the insertion of the stent into the carotid artery is calculated, and the concentration of the force at both ends of the stent is confirmed. Guidelines are presented to modify the stent shape based in order to remove this force concentration which may provoke the neointimal hyperplasia. The methods described in the present paper are easily applied to the shape design of stents and will be an effective tool for improving the stent shape.

Design method of self-expanding stents suitable for the patient's condition.

A medical device of mesh-shaped tubular structure, called a stent, is frequently used to expand the stenosis of a blood vessel. The stent normally has the structure of longitudinally repeated wavy wire parts and strut parts, and its mechanical properties, such as bending flexibility and rigidity in the radial direction, mainly depend on the shape of the wavy wire and the construction of the strut. This paper presents, a design support system for self-expanding stents that can design stent shape and evaluate stent performance as routine flow. A two-stage method for designing suitable stent shapes is built into this system. The mechanical properties of self-expandable stents are evaluated using a non-linear finite element method. The wire length of the stent and the wire width are adopted as design parameters, and the sensitivity of the mechanical properties to these parameters is obtained. When the patient's conditions, such as blood vessel type and the diameter of the blood vessel with stenosis, are given by medical examination, the performance of the stent in restoring blood flow has to be determined. Finally, a method is proposed for designing suitable stents with the desired performance on the basis of mechanical properties.