Loss of wall stress homeostasis in ascending thoracic aortic aneurysm: histomorphometric insights into patient variants

Abstract: Histomorphometric differences in cell-matrix properties were analysed between ascending thoracic aortic aneurysm (ATAA), dissection (ATAAD) and non-aneurysmal patients, as well as across the circumference of the aneurysms in ATAA cases. Fresh anterior aortic wall samples were collected during surgery. A significant radius-to-intima-media thickness (IMT) ratio variation was observed among ATAA patients, indicating patient-specific adaptive responses. The radius-IMT ratio was significantly lower in ATAAD patients. The quantity and quality of elastin and the quantity of collagen were particularly reduced in ATAAD compared to ATAA and non-aneurysmal aortas. Matrix degradation was accompanied by an increase in the density of vascular smooth muscle cells (VSMCs), albeit with reduced expression of VSMC contractile markers (calponin and α-smooth muscle actin (α-SMA)). Concomitantly ATAA and ATAAD samples exhibited increased markers (matrix metalloproteinase (MMP)-2/9) of proteolysis. Based on radius-IMT ratios we roughly identified ‘thickening’ and ‘thinning’ (i.e. hypertrophic and hypotrophic) aneurysm variants to capture the substantial variation in the loss of mechanical homoeostasis in ATAA. Interestingly we did not find conspicuous differences along the circumference of excised aneurysms in ATAA, except for an increased IMT heterogeneity in ‘thinning’ aneurysms. We conclude that during aneurysm formation wall stress homoeostasis may remain partially intact, particularly in ‘thickening’ ATAA. Our study underscores the current critique that aneurysm dimensions are poor risk predictors; therefore there is a crucial need for better-informed preventive intervention in ATAAD. (Figure presented.). Key points: Ascending thoracic aortic aneurysm (ATAA) variants can be categorised as aortic medial thickening (hypertrophic) or aortic medial thinning (hypotrophic) based on the radius-to-intima-media thickness (IMT) ratio, reflecting distinct disruptions in mechanical homoeostasis. Morphological patterns arise from dynamic interactions in the aortic medial layer between vascular smooth muscle cells (VSMCs) and the extracellular matrix (ECM). Increased number of synthetic VSMCs in the medial layer of ATAA patients is a compensatory response to maintain vessel elasticity and structural integrity. In acute type A aortic dissection (ATAAD) aortas with medial thinning are characterised by ECM breakdown and maladaptive remodelling. ATAA development is circumferentially homogeneous, despite the occurrence of inter- and intrapatient variability in vascular architecture, composition and VSMC characteristics.