Correspondence on: “Therapeutic Prospect of Adipose-Derived Stromal Cells for Treatment of Abdominal Aortic Aneurysm”

We are quite interested in the important review by M. Parvizi and M.C. Harmsen, published on February 23, 2015, in Stem Cells and Development [1]. The authors pointed out that studies failed to explain the initial trigger and initiation of abdominal aortic aneurysm (AAA) in animal studies. The typical chicken or egg question also arouses our enormous interest. To answer this question, we successfully induce a novel model of enlarging AAA in rabbits by a combination of elastase incubation and aortic coarctation [2]. Our model successfully overcomes the self-healing phenomenon in elastase-induced AAA and indicated that hemodynamic change is vital to the initiation and progression of AAA by a certain mechanism. The onset of AAA diseases involves the activation of the endothelial cells [1]. A decreased endothelial recovery was shown in our experiment; perhaps, endothelial cells are vital to the initiation of AAA under the influence of hemodynamics.

The authors pointed out that smooth muscle cells (SMCs), the main workhorse of an artery, not only serve a contractile role but in addition produce, deposit, and continuously remodel the vascular extracellular matrix. We quite appreciate this point and hypothesize that SMCs account for self-healing of AAA model. In our previous studies, matrix metalloproteinase (MMP)2 kept moderate expression during a 5-month follow-up [3], and a similar expression was shown in enlarging AAA; however, the increased expressions are not proportionate to the enlargement of AAA. Aneurysm develops after infusion of elastase due to an inflammatory cascade that ultimately leads to matrix degradation by MMPs. This classical theory indicates that MMPs play an evil role in AAA formation, and it seems scientific to treat AAA by inhibiting MMPs. However, we hypothesize that MMPs, especially MMP2, play a positive role in the complex remodeling of aneurysmal wall, which then cause a self-healing of AAA. Shen et al. found that MMP2 plays two opposing roles in aortic wall remodeling [4]. Interestingly, so many treatments, including the MMP inhibitor, achieved perfect results in animal studies; however, few are of benefit to human AAA diseases. It seems more reasonable to treat AAA by enhancing the repair progress of aneurysmal wall, such as promoting SMCs adjacent to aneurysm migration and proliferation to some rational degree. Besides, the “response to injury” hypothesis suggests that SMCs migrate and subsequently proliferate after injury, and the contractile SMCs be modulated back into the synthetic phenotype and participate in tissue repair [5]. It seems feasible and beneficial to promote and restore the phenotype of the affected medial SMCs.