Letter regarding "interference of doxycycline pretreatment in a model of abdominal aortic aneurysms".
To the editor,We are quite interested in the important article by Mata and col-leagues, published on November 5, 2014, in Cardiovascular Pathology [1].Their research indicates that pretreatment with doxycycline via gavage(30 mg/kg per day) inhibited the activity of matrix metalloproteinases(MMP) and the inﬂammatory response, and may play an important rolein the prevention of the development of abdominal aortic aneurysm(AAA). Of note, this conclusion was drawn in a novel enlarging AAAmodelinrats,notinatraditionalrat modelinducedbyelastaseperfusion.We drew inspiration from the authors' research and hypothesizedthat hemodynamic change caused by coarctation is vital to the progres-sionofAAA.NovelrabbitAAAmode lwasinducedandenlargedprogres-sively after a combination of low concentration elastase incubation andaortic coarctation [2], which successfully overcomes the self-healingphenomenon reported by Origuchi and colleagues [3].Itisexcitingbutalso confusing for us that the authors achieved perfect results in thischallenging rat AAA model. Interestingly, the authors showed a typicalAAA with a dramatic large diameter in Fig. 1A and B at 3 dayspostsurgery, and the diameter did not increase signiﬁcantly from Day 3to Day 15. In our rabbit AAA model, a dilatation ratio of more than311% was seldom found even by Week 16, and the diameter enlargedgradually during follow-up. Can the authors please comment on this?Aneurysmdevelopsafterinfusionofelastaseduetoaninﬂammatorycascade that ultimately results in matrix degradation by MMPs. ThisAAA model indicates that MMPs play an “evil” role in AAA formation,anditisscientiﬁctopreventAAAbyinhibitingMMPs.Theenlargementoftheaortacoincideswithinﬂammatorycellinﬁltrationafewdaysafterinfusionin thismodel[4]. We speculate that aneurysmismainly duetothe expansion of the weakened wall when exposed to pulsatile bloodﬂow, and inﬂammatory cell inﬁltration is the result of damage to theaorta by chemical corrosion rather than cause of AAA progression.MMP9-positive staining and macrophages in ﬁltration were shown inthe elastase-incubated aorta by Week 2. However, both expressionsdecreased dramatically thereafter [5]. MMP2 expression increased afterelastase exposure and kept moderate expression during a 5-monthfollow-up [5]. These similar expressions were also seen in our enlargingAAA model; however, the increased expressions are not proportionate tothe enlargement of AAA. It seems that hemodynamic change plays a vitalrole in the progression of AAA rather than endogenous MMPs. MMP2plays an important role in smooth muscle cell (SMC) migration andproliferation, which may account for the self-healing seen in an elastase-induced AAA model in rabbits. Endogenous MMPs, such as MMP2 andMMP9, are important to the complex remodeling process.It is maybe confusing and contradictory to inhibit MMPs foraneurysm treatment. It seems more reasonable to treat AAA byenhancing the repair progress of aneurismal wall, such as promotingSMC migration and proliferation to some rational degree, which mayneed to up-regulate MMPs expression rather than down-regulatethem. We look forward to the authors' comments.Yonghua BiDepartment of Interventional RadiologyThe First Afﬁliated Hospital of Zhengzhou UniversityZhengzhou 450052, ChinaDepartment of RadiologyThe First Afﬁliated Hospital of China Medical UniversityShenyang 110001, ChinaKey Laboratory of Diagnostic Imaging and Interventional Radiology ofLiaoning Province, Shenyang, ChinaHongshan ZhongKe Xu