Atsushi Mahara

This study aimed to establish a noninvasive magnetic resonance angiography (MRA) framework for monitoring tumor vascular adaptation longitudinally using the intravascular supramolecular contrast agent 8-arm PEG-FGd₃. (1) Unlike conventional Gd-chelates, which predominantly enhanced tumor tissue because of contrast extravasation, 8-arm PEG-FGd₃ provided high-contrast delineation of tumor-feeding vessels and microvascular architecture, visualizing tumor vessels as small as 190 μm. (2) This is the first instance of defining neovascularization patterns in superfine MRA images. (3) The longitudinal atlas of tumor vessels varied over time. In the fast-growing stage, both tumor doubling time and vessel doubling time were positive, vessels initiated neovascularization processes such as vessel co-option-like appearance, sprouting-like appearance, and elongation-tortuosity-like change. In the slow-growing stage, vessel doubling time turned negative, vessels became more structured, with continued elongation-tortuosity. Vessel remodeling followed vascular disruption rapidly. In the shrinkage stage, vessel loss preceded tumor shrinkage. (4) Seven days post-ligation, there were more vessels than the second day. ANG2 also showed a increasing tendency during this period, while VEGF was decreasing but still higher than that in the tumor without ligation, although there was no significant difference.

The plasticity of blood mononuclear cells (MCs) and their role in vascular remodeling have been the focus of many studies; however, their in vitro differentiation efficiency remains poorly understood. Herein, we demonstrate that the inflammatory response accelerates the efficiency of MCs differentiation into endothelial-like cells through chemical cues in vitro . RT-PCR and RNA sequencing revealed that the differentiated cells exhibited upregulated pathways associated with vascular remodeling and regeneration. In contrast, MCs collected from normal blood showed a differentiation bias toward macrophages. Notably, under inflammatory conditions, primarily monocytes transitioned into the CD14++/CD16+/CD163+ subset, which contributed significantly to vascular remodeling. This transition was triggered by inflammation, as confirmed by in vitro cytokine treatment.

Expanded polytetrafluoroethylene (ePTFE) is a widely used material in diverse medical devices, particularly in the cardiovascular system, owing to its chemical stability and suitable mechanical properties. However, the chemical inertness makes surface modification difficult. In the present study, modification of ePTFE with a peptide was successfully achieved based on a unique photoreaction technique. We previously screened the hemocompatible peptide (HCP), histidine-glycine-glycine-valine-arginine-leucine-tyrosine (HGGVRLY), with high endothelial affinity and antiplatelet ability as modifying molecules. We synthesized a photoreactive peptide by combining a phenylazide group with the HCP, which was subsequently immobilized on the ePTFE surface through a short UV exposure time after argon plasma (Ar) treatment. Cross-sectional images of the surface modified with fluorescent-labeled photoreactive HCP showed efficient modification even within the pores of ePTFE. In vitro assessment revealed that modification improved the endothelial affinity of ePTFE approximately 5-fold while preventing platelet adhesion and aggregation. The ePTFE grafts were further implanted into an in situ porcine closed-circuit system for the blood contact assessment. Comparative investigations with untreated ePTFE grafts indicated that the modified ePTFE surface attracted more cells positive for CD14, CD16, CD34, and macrophage markers while concurrently exhibiting reduced platelet adhesion. In conclusion, photoreactive HCP proved to be a simple and effective strategy for modifying the ePTFE surface, resulting in enhanced hemocompatibility characterized by increased endothelial and monocyte recruitment as well as antiplatelet attachment on the modified ePTFE graft surface.