from age matched non aneurysmal abdominal aorta may be a superior com parator, in the current study customer reviews this was not a feasible option and thus a limitation. Loss of aortic SMC through apoptosis is a prominent fea ture of AAA disease. The similarity in basal apoptosis we observed between aneurysmal and non aneurysmal SMC concurs with a previous report where no differences were observed between AAA and matched inferior mesen teric artery SMC cultured under standard conditions. However, we noted significantly augmented apoptosis in AAA SMC upon e posure to staurosporine. It is conceiv able that in AAA disease, SMC apoptosis in vivo may be at tributable to a heightened sensitivity to apoptotic stimuli in a significant proinflammatory environment, rather than a difference in basal apoptosis levels.

Accelerated vascular aging, cell senescence and syn thetic SMC phenotypes have been documented in AAA patients or those with risk factors for AAA. Another common feature of aged cells is that of telo mere shortening and this has been demonstrated in both AAA SMC and leucocytes of patients with AAA. Rhomboid SMC are more commonly reported in pathological states and there is speculation that aging causes a general switch towards a synthetic phenotype in vascular SMC. Aging has been demonstrated to alter SMC proliferation in a variety of ways depending on source and model, and also to modulate the prolifer ative response to growth factors or cytokines. In keeping with this concept, we also noted differential sen escence between PCA vehicle treated and CCE SMC, and likewise between human SV and AAA SMC.

It is reasonable to suggest that the SMC phenotypes we iden tify in both the human AAA and porcine CCE are indi cative of accelerated aging. Another defining feature of end stage AAA disease is breakdown of the ECM, with marked degradation of elastin fibres. In addition, collagenase activity is ele vated in AAA tissue. Evidence from pathological specimens suggests that loss of elastin is an early event mediated by SMC and is associated with production of MMP 2 from SMC themselves. Elevated e pression levels of both MMP 2 mRNA and protein have been reported in human and animal AAA tissue. The observed deficiencies in PCA SMC morphology and proliferation after CCE treatment were Carfilzomib also evident at the level of MMP 2 secretion in which we observed, contrary to previous reports, that both basal and phorbol ester stimulated secretion of MMP 2 from CCE SMC was significantly lower than from VEH SMC.

The unpaired nature of AAA SMC and SV SMC precluded a direct comparison between them although we noted that absolute levels of MMP 2 secretion from AAA SMC were consistently selleck chem Volasertib lower than from equivalent densities of SV SMC under identical conditions. Inter estingly, a study using tissue biopsies from the UK Small Aneurysm Trial concluded that MMP 2 may only play an etiopathogenic role in small aneurysms and moreover, significant quantities were bound to the ECM. MMP 2 may actually