Is biological treatment the future of small aneurysms?


Speaking at the International Congress, in Phoenix, AZ, Dr Juan Parodi, Washington University, St Louis, asked whether biological treatment of aneurysms is the third wave after resection and endovascular aneurysm repair?

He began by stating “many years ago we learnt that an aneurysm is not a flat tyre, it is highly active metabolically with ongoing synthesis and degradation of matrix proteins.” He added that the pathophysiology of human abdominal aortic aneurysm (AAA) formation involved multiple factors including: biomechanical wall stress (treated with endografts); inflammation; proteolytic degradation; and genetics. Biopsies of AAAs have found that matrix metalloproteinases (MMPs) 8 and 9 expression was mediated by native mesenchymal cells and was independent of inflammatory infiltrate. Therefore, a localised increase in MMP-8 or MMP-9, mediated by native mesenchymal cells, presents a potential pathway for collagen breakdown and AAA rupture.

Parodi commented that there have been several attempts to use biological solutions, for example the use of growth factors to promote tissue encapsulation of stents or endografts. In addition, attempts have also been made to promote myointimal hyperplasia with the use of bare metal or absorbable stents. Finally, there has also been some use of biological manipulation with the use of MMP inhibitors, enhancement of TIPS, anti-inflammatory drugs and anti-oxidants.

Regarding myointimal hyperplasia , Parodi has analysed data on 36 patients who had survived for more than five years after endoluminal treatment of an AAA using the initial Parodi model. He found that there were no increases in neck diameter. Of the four specimens studied it was found that myointimal hyperplasia was very significant (0.7). Based on this study, Parodi began an experimental pilot study to examine myointimal hyperplasia prevents dilatation of the neck of AAAs. A preliminary study involved inducing AAAs in mice (with the application of Elastase or calcium chloride). The study found that aneurysm formation was prevented with the introduction of myointimal hyperplasia .

Next, Parodi discussed the use of MMP inhibitors such as Doxycyclin, Rapamycin, Simvastatin as well as ACE inhibitors. “Is a super pill coming to put us out of business?” he asked. The evidence so far shows that Doxycyclin and statins have been effective in animals and that Doxycyclin produced a reduction in blood concentration in MMP-9 and MMP-2. In addition, Doxycyclin and statins reduced MMP activity on the aneurysmal wall.

Parodi concluded that current therapies for aneurysms are based on mechanical treatment, “however, with an increased knowledge of the biochemical mechanisms for aneurysm expansion, it may be possible to prevent the growth of small aneurysms in the future.”