in 2 fold increase in MMP 2 secretion although the absolute levels secreted from the CCE cells were lower than VEH. Consistent with porcine selleck chemicals Imatinib cells, human SMC secreted MMP 2 basally and this was further increased by TPA stimulation in both SV and AAA. MMP 9 secretion was not detected under any condi tion in porcine or human SMC, either basally or with TPA stimulation. Discussion This study has revealed a number of key findings. Firstly we maintained viable porcine carotid arteries under flow conditions in a bioreactor model for 12 days. Histo logical e amination revealed that vessel wall architecture in control vessels was identical to that of freshly isolated PCA, but protease pre treatments either indi vidually or combined, led to visible disruption of the ar terial wall.

Within the time frame studied and under these conditions we did not however, observe an unam biguous dilatation of the vessel although we speculate that the thinning we observed preceded overt dilation which may well become apparent at a later time point. Secondly, viable cells were cultured from all vessels and confirmed as SMC through co e pression of SMA and SM MHC. All porcine SMC e hibited characteristic spindle morphology with the e ception of those cultured from the combined protease treated vessels that were more rhomboid, a trait common to dedifferentiated, often pathological SMC. The aberrancies in PCA SMC morphology evident after treatment with CCE were recapitulated in SMC from end stage human AAA tissue. In agreement with a previous report, AAA SMC were morphologically distinct from SV SMC and also from the aortic SMC obtained from a commercial source.

SMC phenotypic switching underlies their unique abil ity to elicit compensatory responses to vascular injury. Indeed, increased SMC proliferation is a prominent fea ture of occlusive vascular diseases. Conversely, it is well established that SMC depletion is a hallmark of AAA, which might suggest functional inability of the SMC to remodel the degenerating aortic wall. In this study we revealed that AAA SMC consistently prolifer ated more slowly than non aneurysmal SV SMC cultured from age and se matched patients. Similarly, the prolifer ative capacity of SMC was reduced to a similar degree in porcine CCE SMC compared with paired VEH cells. Re ports relating to proliferative capacity of AAA SMC com pared to non aneurysmal SMC are at variance.

claims of both increased and decreased proliferation have been documented. In the latter, AAA SMC consist ently proliferated by up to 70% less than inferior mesenteric artery SMC, comparator GSK-3 cells that were cultured from the same patients. In the current study we e amined SMC from AAA and SV sources from a total of 24 different pa tients. Given our e pertise and familiarity with inherent variability between individual patients and our documented evidence supporting the intrinsic heterogen eity of SMC populations, this is an important Tubacin 537049-40-4 aspect of the current study. Whilst SMC derived