Plaque regression is very difficult in patients with atherosclerosis. Lipid-lowering drugs including the powerful inhibitors of proprotein convertase subtilisin kexin-like 9 (PCSK9) could only reduce the mean change in percent atheroma volume of coronary plaque by less than 3% [11], while the plaque regression of grafts rapidly reached to 60% in our aortic arch transplantation mouse model, indicating that this model is a powerful tool to investigate the mechanisms of plaque regression. Atherosclerotic plaque formation usually results from a complex interplay between many factors such as lipid deposition, inflammatory immune reaction, cell migration, and arterial wall injury. However, the mechanisms of plaque regression are largely unknown. Besides to reduce the lipid burden, targets for changing plaque environment should make important contributions to plaque regression. Functional restoration of the endothelium, reversion of the proliferative synthetic vascular smooth cells [12], and mobilization of anti-plaque macrophages [13] have been reported to promote plaque regression. Characterized by dramatically regression of atherosclerotic plaque, the aortic arch transplantation model can be employed to search therapeutic targets for plaque regression.

The mouse atherosclerosis regression model through aortic arch transplantation was first reported by Fisher et al. in 2003 [1]. Unfortunately, few laboratories have employed this model to research plaque regression since then, which may be attributable to the technique difficulty of the transplant surgery and insufficient details of the procedure to facilitate duplication. Therefore, we tried to provide a more detailed, easily reproducible surgical protocol to facilitate the duplication of this model.

Separation of the abdominal aorta from IVC is a basic skill and very important. The purpose of separation is to increase the visual area of the abdominal aorta and expand the operable space for subsequent suture. A key point for this step is to find and ligate the small branches hidden between the aorta and vein to avoid active bleeding, shock, and thrombosis. Different from the thoracoabdominal aortic transplantation model which needs a 4 mm segment separation of abdominal aorta, the aortic arch transplantation model requires a 7 mm or longer segment separation for end-to-side anastomosis. In that case, it is inevitable to separate the abdominal aortic segment below the lumbar artery, where the aorta and vein are tightly held together by transparent connective tissue, while incautious manipulation-induced arteriovenous rupture and bleeding would hardly be stopped. We summarized 4 steps to guarantee the successful separation of the abdominal aorta as follows: starting below the left renal vessels, gently tearing the connective tissue, bluntly dissecting it, injecting saline to increase exposure, threading, and knotting the branches.

How to make abdominal aortotomies is critical for the success rate of arch transplantation. In thoracoabdominal aortic transplantation, transecting the abdominal aorta at the appropriate location can directly obtain two elliptical openings with the trim edge. However, making incisions for aortic arch transplantation requires some microsurgical skills. Here we introduced a method of abdominal aortotomies inspired from mouse heart transplantation [14]. By using a needle of 10–0 nylon suture, we could cut out a section of the anterior aortic wall and the incision presented an ellipse with the trim edge, which greatly reduced the incidence of the incision closure.

Anastomosis is the most critical step of transplantation. The success rate may be improved by modifying the order of proximal to distal anastomosis and anastomosis method. After adjusting the order of anastomosis to distal–proximal, the full arterial segment would facilitate the puncture of the abdominal aorta to avoid damage to the posterior aortic wall. Moreover, the elastic aortic wall was conducive to the puncture of the stitching needle when anastomosis, without tearing the wall due to tension. For traditional anastomosis, stay sutures are placed at the 6 and 12 o’clock positions for the purpose of aligning the edges of the opening and incision to prevent large leakages caused by misalignment, but in this way, the opening and incision are sticking to each other, the exit point of stitching needle is often mistaken and it is easy to run the stitching needle through the left and right cut edge of the opening or incision, causing direct closure of them and occlusion of blood flow. Therefore, we recommended that the stay suture at 6 o’clock position should not be knotted until the left cut edge was closed, by which the space between the opening and the incision was open and the entry and exit point of the stitching needle could be visualized without mistake. What’s more, the running sutures were not pulled tight until the third stitch was finished, which was also based on this consideration.