The Clinical Analysis Of Revascularization Of The Visceral Vessels In Complex Aortic Aneurysms And The Basic Research On Biological Repairing Of The Aortic Aneurysm Wall

Objective: Aortic aneurysm refers to a disease of the dilated aorta.Its onset is hidden,but the fatality rate is extremely high once the aneurysm ruptured.At present,there are still challenges in the surgical and non-surgical treatment of aortic aneurysms.Surgical treatment can reduce the risks of aneurysm rupture to a certain extent for patients who have the indications for intervention.Fenestrated and branched stent-grafts are the first choice for reconstruction of the visceral arteries of aortic aneurysms,but for some complex aortic aneurysms,these methods still have great limitations.Moreover,for aortic aneurysms that have not yet reached the indications of surgical intervention,the available intervention treatment is limited.For patients who have not yet reached the indication of surgical intervention,intervention methods have great limitations.In the study,we firstly retrospectively analyzed the cases who received endovascular surgeries using the retrograde branched extension limb assembling(REBEL)technique in our center,with the aim to verify the safety and effectiveness of this new method of revascularization of visceral branch arteries in complex aortic aneurysms.For aortic aneurysms that have not yet met the indications for surgical intervention,we explored the repairing mechanism of aortic aneurysm wall from the perspective of biology with the aim to provide a new therapeutic target for non-surgical treatment of aortic aneurysm.Methods: Firstly,the study retrospectively included 23 consecutive patients undergoing total endovascular repair with the retrograde branched extension limb assembling technique from August 2014 to January 2019.The patients were unsuitable for treatment with current off-the-shelf devices or required emergent repair.The evaluated outcomes were technical success,operative mortality,complication morbidity,late survival,endoleakage,and reintervention during follow-up.Secondly,based on our previous research results,we explored the mechanism of Fibroblast Growth Factor 18(FGF18)and integrin β1 involved in the biological repair of aortic aneurysm wall.Stable rat arterial endothelial cell line and aortic smooth muscle cell line with low expression and high expression of integrin β1 were established by lentiviral transfection.Different concentrations of FGF18 were used to stimulate the rat endothelial cells and smooth muscle cells to detect the expression of elastin component protein in different cell lines.And the corresponding changes in cell proliferation and migration functions were explored.In animal experiments,we established a rat model of abdominal aortic aneurysm,and promoted the high expression of integrin β1 in the aortic aneurysm wall tissue through lentiviral transfection.While giving FGF18 stimulation,the changes in the aneurysm wall tissue were observed by immunohistochemistry and tissue staining,and the mechanical changes of the aneurysm tissue were evaluated by mechanical testing.Results: In clinical retrospective analysis,the REBEL technique is safe and effective for reconstruction of the visceral arteries.There were no aortic rupture related deaths and no target vessel occlusion during the follow-up period.In the basic research of biological repair of aneurysm wall,we found FGF18 can promote the high expression of elastic fiber components in rat artery endothelial cells in a time-dependent and concentration-dependent manner.But there is no such effect in the normal smooth muscle cells.In the rat arterial endothelial cell line with high expression of integrin β1 and the rat aortic smooth muscle cell line with high expression of integrin β1,the above-mentioned effects of FGF18 were enhanced.FGF18 can promote the proliferation and migration of rat arterial endothelial cells and smooth muscle cells with high expression of integrin β1.In animal experiments,the high expression of FGF18 combined with integrin β1 can promote the repair of aneurysm wall in the rat abdominal aortic aneurysm model.Mechanical testing indicates that its tensile strength has also been significantly enhanced.Conclusions: There are still great challenges in the treatment of complex active tumors both surgically and none-surgically.In terms of surgical treatment,the REBEL technique is a feasible option with acceptable results for complex aortic aneurysms in absence of endovascular equipment or emergency situations.In terms of non-surgical treatment,biological repair can delay the progression of aortic aneurysm disease to a certain extent for aortic dilated diseases that have not yet reached the indications of surgical treatment.In this study,we found that FGF18 combined with integrin β1 overexpression can promote the biological repair of aortic aneurysm wall tissue.It is expected to provide a new therapeutic target for delaying the progression of aortic aneurysm disease and promoting the biological repair of aneurysm wall.This study summarized and explored the surgical treatment and non-surgical biological repair of complex aortic aneurysms from the perspectives of surgical treatment and biological repair and provided a new idea for the comprehensive treatment of aortic aneurysms and dilated aortic diseases.