The Effect of Immunosuppression on Aortic Dilatation in a Rat Aneurysm Model

Abstract

This study was conducted to investigate whether systemic immunosuppression attenuated aortic dilatation in a rat aneurysm model. Sprague-Dawley rats were subjected to elastase infusion of the infrarenal aorta and divided into two groups of 12 rats each. The immunosuppression group (group 1) was given subcutaneous injections of cyclosporine A (5 mg/kg per day), azathioprine (2 mg/kg per day), and methylprednisolone (2 mg/kg per day) from the operative day until postoperative day (POD) 6. An additional subcutaneus injection of cyclophosphamide 30 mg/kg was also given on the operative day. The control group (group 2) was given subcutaneous injections of saline. Relaparotomy was performed on POD 7. After measurement of the aortic diameter, aortography and ultrasonography were performed in three rats from each group, following which the aortas were excised for histologic examination. The aortic diameter was significantly smaller in group 1 (2.58 +/- 0.37 mm) than in group 2 (6.21 +/- 1.74 mm) (P < 0.01) and the aortic lumen was slightly dilated in group 1, whereas it was spherically dilated in group 2. Total loss of elastic tissue was seen in both groups. Inflammatory cell infiltration and collagen fiber fragmentation were noted in group 2, whereas very little inflammatory cell infiltration and well-preserved collagen fibers were seen in group 1. These findings showed that immunosuppression attenuates aortic dilatation, partly by preserving the collagen fibers, in this rat aneurysm model.

Long Term Stabilization of Expanding Aortic Aneurysms by a Short Course of Cyclosporine A through Transforming Growth Factor-Beta Induction

“…In parallel with the enhanced TGF-beta signaling, our results show that CsA administration prevents aneurysmal degeneration in two rodent models of AAA, as previously evoked using a cocktail of immunosuppressive drugs including CsA in the rat elastase model [19]. Of interest, CsA treatment in our study stabilized the diameter of formed, expanding AAAs in rats.…”

Concomitant coiling reduces metalloproteinase levels in flow diverter-treated aneurysms but anti-inflammatory treatment has no effect

“…Anti-inflammatory and immunosuppressive drugs such as ciclosporin A have proved to be beneficial on MMP levels in abdominal aneurysms 38 50 51. However, in our study, the expression levels of MMP2 and MMP9 in the group treated with FD + ciclosporin were comparable to those in aneurysms treated with FD alone, with higher levels of active-MMP9.…”

Expression of annexin II in experimental abdominal aortic aneurysms

“…Thus, we were not able to develop a model that had different levels of elastic tissue degeneration over time. Based on previous studies, there is a lack of consensus on the time course of elastin fiber degeneration in the elastase-induced AAA rat model [21,23,24].…”

“…Male Wister rats weighing about 300 g were anesthetized and underwent laparotomy under sterile conditions [18][19][20][21]. Briefly, the abdominal aorta was isolated from the level of the left renal vein to the bifurcation.…”

“…To overcome this problem, we have used an elastase-induced rat aortic aneurysm model in the present study. Since this model shares many important features with human AAAs, many laboratories have used this model to investigate the pathogenesis of aneurysm formation [18][19][20][21].…”