Spatiotemporal mapping of matrix remodelling and evidence of in situ elastogenesis in experimental abdominal aortic aneurysms.

Abstract

Spatiotemporal changes in the extracellular matrix (ECM) were studied within abdominal aortic aneurysms (AAAs) generated in rats via elastase infusion. At 7, 14 and 21 days post-induction, AAA tissues were divided into proximal, mid- and distal regions, based on their location relative to the renal arteries and the region of maximal aortic diameter. Wall thicknesses differed significantly between the AAA spatial regions, initially increasing due to positive matrix remodelling and then decreasing due to wall thinning and compaction of matrix as the disease progressed. Histological images analysed using custom segmentation tools indicated significant differences in ECM composition and structure vs healthy tissue, and in the extent and nature of matrix remodelling between the AAA spatial regions. Histology and immunofluorescence (IF) labelling provided evidence of neointimal AAA remodelling, characterized by presence of elastin-containing fibres. This remodelling was effected by smooth muscle α-actin-positive neointimal cells, which transmission electron microscopy (TEM) showed to differ morphologically from medial SMCs. TEM of the neointima further showed the presence of elongated deposits of amorphous elastin and the presence of nascent, but not mature, elastic fibres. These structures appeared to be deficient in at least one microfibrillar component, fibrillin-1, which is critical to mature elastic fibre assembly. 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. Copyright © 2014 John Wiley & Sons, Ltd.