We introduced the vascular remodeling mouse system induced by the wire injury to investigate the molecular and cellular mechanisms of cardiovascular diseases. Using these models, we focus on the adventitial cell population in the outermost layer of the adult vasculature as a vascular progenitor niche. Firstly we used the standard wire injury approach, leaving the wire for 1 min in the artery and retracting the wire by twisting out to expand the artery and denude the inner layer endothelial cells in the both peripheral artery and femoral artery. This method leads to adventitial lineage cell accumulation on the medial–adventitial border, but no contribution into the hyperplastic neointima. Since advanced atherosclerotic plaques in the mouse models and human clinical specimens show the elastic lamina in the media broken, we hypothesized that adventitial lineage cells contribute to acute neointima formation induced by the mechanical damage in both endothelial and medial layers. To make this intensive damage, next, we used the bigger diameter wire with no hydrophilic coating and repeated the ten-times insertion and retraction of the wire after leaving for 1 min in the femoral artery. The additional ten-times intensive movements of the wire lead to breakdown and rupture of the elastic lamina together with a contribution of adventitial lineage cells to the hyperplastic neointima. Here we describe these two different wire injury methods to induce different types of vascular remodeling at the point of adventitial lineage cell contribution to the hyperplastic neointima by targeting two separate locations of hind limb artery, the peripheral artery and femoral artery, and using two different diameter wires.
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We thank Microscope Core for the confocal microscope support and CCMS for the mouse husbandry care (Icahn School of Med at MSSM). We thank D. Yang (Icahn School of Med at MSSM) for the initial technical introduction and S. Hong (NHGRI) for the initial technical training of peripheral artery wire injury. We are grateful to Professor M. Sata (Tokushima Univ.) who established femoral artery wire injury technique originally for sharing information, and H. Kato (Tokyo Univ.) for the technical advice.
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