We used a mouse model of postnatal ascending aortic aneurysms ( Fbln4<sup>SMKO</sup>; termed SMKO [SMC-specific knockout]), in which deletion of Fbln4 (fibulin-4) leads to disruption of the elastin-contractile units caused by a loss of elastic lamina-SMC connections.
Aortic diameter in the DM+AA group was less than that in the AA group, and elastin fragmentation grade of the aortic wall was reduced in the DM+AA group.
BM-MSCs and MSCs-CM significantly attenuated matrix metalloproteinase (MMP)-2 and MMP-9 expression, aortic elastin degradation and AA growth at the site of AA.
Interestingly, the elastin-contractile unit, which is an anatomical and functional unit connecting extracellular elastic laminae to the intracellular SMC contractile filaments, via cell surface receptors, has been shown to play a critical role in the mechanosensing of SMCs, and many genes identified in TAAs encode for proteins along this continuum.
Elastin and collagen fibers were more highly aligned in BAV-NA and BAV-TAA cases than in TAV-TAA cases, whereas TAV-TAA cases were more disorganized than TAV-NA cases.α-Elastin content was unchanged.
CAM suppressed the progression and rupture of AA through the suppression of inflammatory macrophage infiltration, a reduction in MMP-2 and MMP-9 activity, and the inhibition of elastin degradation associated with the suppression of NF-κB phosphorylation.
The substantial production of elastin and elastic fibre-like structures that we observed in the AAA neointima, which was not observed elsewhere within AAA tissues, provides a unique opportunity to capitalize on this autoregenerative phenomenon and direct it from the standpoint of matrix organization towards restoring healthy aortic matrix structure, mechanics and function.
Taking into consideration the continuously ongoing challenges during life, there is a physiological degradation of elastin into elastin-derived peptides which is accentuated in several disease states such as obstructive pulmonary diseases, atherosclerosis and aortic aneurysm.