Summary Blood and lymphatic vessels surrounding the heart develop through orchestrated processes from cells of different origins. In particular, cells around the outflow tract which constitute a primordial transient vasculature, referred to as aortic subepicardial vessels, are crucial for the establishment of coronary artery stems and cardiac lymphatic vessels. Here, we revealed that the epicardium and pericardium-derived Semaphorin 3E (Sema3E) and its receptor, PlexinD1, play a role in the development of the coronary stem, as well as cardiac lymphatic vessels. In vitro analyses demonstrated that Sema3E may demarcate areas to repel PlexinD1-expressing lymphatic endothelial cells, resulting in proper coronary and lymphatic vessel formation. Furthermore, inactivation of Sema3E-PlexinD1 signaling improved the recovery of cardiac function by increasing reactive lymphangiogenesis in an adult mouse model of myocardial infarction. These findings may lead to therapeutic strategies that target Sema3E-PlexinD1 signaling in coronary artery diseases.

Vascular endothelial cells (ECs) in angiogenesis exhibit inhomogeneous collective migration called “cell mixing”, in which cells change their relative positions by overtaking each other. However, how such complex EC dynamics lead to the formation of highly ordered branching structures remains largely unknown. To uncover hidden laws of integration driving angiogenic morphogenesis, we analyzed EC behaviors in an in vitro angiogenic sprouting assay using mouse aortic explants in combination with mathematical modeling. Time-lapse imaging of sprouts extended from EC sheets around tissue explants showed directional cohesive EC movements with frequent U-turns, which often coupled with tip cell overtaking. Imaging of isolated branches deprived of basal cell sheets revealed a requirement of a constant supply of immigrating cells for ECs to branch forward. Anisotropic attractive forces between neighboring cells passing each other were likely to underlie these EC motility patterns, as evidenced by an experimentally validated mathematical model. These results suggest that cohesive movements with anisotropic cell-to-cell interactions characterize the EC motility, which may drive branch elongation depending on a constant cell supply. The present findings provide novel insights into a cell motility-based understanding of angiogenic morphogenesis.

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Stretching of the VIIIth nerve should be avoided to prevent postoperative hearing impairment. Adequate exposure of the lower cranial nerve roots and lateral medulla oblongata from the caudal side without using the brain retractor gives enough space for decompression with minimum stretching of the VIIIth nerve. Maximum preservation of the arachnoid membrane along the VIIIth nerve and shortening of the duration of microscopic manipulation may help in avoiding postoperative hearing impairment.

Background:Giant thrombosed vertebral artery aneurysms (GTVAs) are difficult disease to treat. Here, we are reporting a case of GTVA successfully treated with excluding the pathological segment and restoring the anterograde blood flow of the parent artery, highlighting the reliable surgical procedure.Case Description:A 55-year-old man with a left GTVA complained of right hemiparesis (manual muscle testing 4/5) represented by hand clumsiness and gait disturbance, in addition to severe left-sided dysesthesia, was referred to our hospital. The posterior inferior cerebellar artery (PICA) was incorporated into the GTVA segment, and the contralateral vertebral artery showed atherosclerotic change. Thus, we decided to treat the aneurysm with aneurysm trapping and thrombectomy, in conjunction with V3-radial artery graft (RAG)-V4 bypass and occipital artery (OA)-PICA bypass through a suboccipital transcondylar approach. The distal end of the dilated segment was meandering and deflecting outwardly to the vicinity of the internal auditory canal and was stretched in an axial direction. Thus, the V4 stump can be transposed to the triangle space made by the medulla, lower cranial nerves, and sigmoid sinus, and we could perform a safe and reliable anastomosis through the corridor. After the surgery, the compression of the brain stem was released, and right hemiparesis was improved completely after rehabilitation. The patient was discharged with a modified Rankin Scale score of 1.Conclusion:Trapping of the aneurysm and thrombectomy are the most radical treatment for GTVA, and if possible, reconstruction of anterograde blood flow with V3-RAG-V4 bypass and OA-PICA bypass is desirable.