Biomechanical properties of the thoracic aorta in Marfan patients

Abstract

Background: Marfan syndrome (MFS), a genetic disorder of the connective tissue, has been strongly linked to dilation of the thoracic aorta, among other cardiovascular complications. As a result, MFS patients frequently suffer from aortic dissection and rupture, contributing to the high rate of mortality and morbidity among MFS patients. Despite the significant effort devoted to the investigation of mechanical and structural properties of aneurysmal tissue, studies on Marfan aneurysmal biomechanics are scarce. Ex vivo mechanical characterization of MFS aneurysmal tissue can provide a better insight into tissue strength outside the physiologic loading range and serve as a basis for improved risk assessment and failure prediction. Methods:The mechanical and microstructural properties of MFS aneurysmal thoracic aorta (MFS, n=15, 39.5±3.91 years), non-MFS aneurysmal thoracic aorta (TAA, n=8, 52.8±4.9 years), healthy human thoracic aorta (HH, n=8, 75.4±6.1 years), and porcine thoracic aorta (n=10) are investigated. Planar biaxial tensile testing and uniaxial failure testing were utilized to characterize the mechanical and failure properties of the tissue, respectively. Verhoeff-Van Gieson (VVG) and PicroSirius Red stains were utilized to visualize the elastin and collagen fiber architecture, respectively.Results: MFS tissue was found to have age-dependent but diameter-independent mechanical, structural, and morphological properties, also showing extensive elastin fiber degradation. Non-MFS thoracic aneurysmal aorta was thicker and stiffer than age-matched MFS tissue. Moreover, non-MFS thoracic aneurysmal mechanics resembled closely the mechanics of older healthy human tissue. Younger MFS tissue (<40 years) exhibited similar mechanical and structural properties to aged porcine tissue.Conclusions: Both age and aneurysmal presence were found to be factors associated with increased stiffness in aortic tissue, and aortic diameter was not a significant determinant of mechanical property deterioration. Additionally, the presence of MFS was found to induce stiffening of the thoracic aorta, although not to the extent of the non-MFS aneurysm.

Patient-Specific Biomechanics in Marfan Ascending Thoracic Aortic Aneurysms

“…Sparse data exist regarding the failure properties of Marfan aTAA, which is limited to failure stresses in the circumferential direction and ranged from 630 kPa in older Marfan patients (age >40 years) to 1200kPa in younger Marfan patients (age <40 years). 17 In our study, 3 patients had circumferential stresses greater than 600 kPa, which would have put them at risk for possible dissection. In comparison, mean tensile strength in circumferential direction for TAV-aTAA at failure was 961 kPa, while for BAV-aTAA was 1656kPa, 24 suggesting Marfan tissue is weaker circumferentially than its BAV counterpart and within the range of its TAV counterpart.…”

“…Material properties from published bi-axial stretch testing on surgically resected Marfan surgical aneurysm specimens were used. 17 ZERO-PRESSURE GEOMETRY. CT angiography images used to reconstruct 3D aTAA geometry under in vivo physiologic blood pressure conditions were considered prestressed.…”

“…Unfortunately, only circumferential tensile strength was evaluated in Marfan tissue and not longitudinal tensile strength. 17 Studies of non-Marfan aTAA failure have shown that ultimate tensile stresses at failure were much greater circumferentially than longitudinally. 24 Thus, aneurysm tissue is weaker in the longitudinal direction and a longitudinal break could result in the typical transverse tear seen in acute dissection.…”

A human importin-β-related disorder: Syndromic thoracic aortic aneurysm caused by bi-allelic loss-of-function variants in IPO8

“…25 Compared to agematched controls, TAA-affected individuals exhibit a stiffer mechanical response with aortic biomechanical properties resembling those of a significantly older (''aged'') nonaneurysmal cohort. 27 Given the observed trend toward stiffer ascending aortas in Ipo8 À/À mice (Figure 3) and recurrent prior associations between aortic ECM deterioration and TAA, 2 we evaluated the structural ECM integrity by using histological elastin and collagen staining in ascending aortic sections of 12-(3 Ipo8 À/À versus 3 WT), 24-(3 Ipo8 À/À versus 3 WT), and 52-week-old (3 Ipo8 À/À versus 2 WT) mice. Whereas the collagen content did not differ noticeably (Figure S9A), the elastic fibers were more disorganized and fragmented in mutant males of all age groups as compared to their WT counterparts (p age-combined ¼ 5.2EÀ4) (Figures 4A, 4B, and S9B).…”

A Case Report of Marfan Syndrome Presenting With Atypical Chest Pain: A 28-Year-Old Male With Non-ST-Elevation Myocardial Infarction (NSTEMI)

“…Wild-type Fibrillin-1 helps provide structural support to the aortic walls as an element of microfibrils, and increasing evidence supports its role in ECM homeostasis preventing harmful remodeling [ 1 ]. In Marfan syndrome, the aorta is rendered less distensible, resulting in structural failure under high stresses rather than elastic distension and appropriate return to its original shape [ 3 , 4 ]. Thus, individuals with Marfan syndrome would be expected to develop structural issues from lower forces within the aorta than those with a normal genotype and undergo remodeling predisposing the tissues to structural failure at an increased rate compared to individuals without dysfunctional Fibrillin-1.…”