Differential Impact of Wall Shear Stress on Aortic Tissue Properties in Thoracic Aneurysms: Insights from Tensile Testing and Gene Expression Analysis

Background: Recent 4-D MRI studies have revealed altered blood flow patterns in thoracic aortic aneurysms (TAA), resulting in increased wall shear stress along the outer curvature of the ascending aorta. This study aimed to characterize the biomechanical properties and gene expression profiles of aortic tissue in such areas of altered wall shear stress in TAA patients and relate these to aortic valve morphology and aneurysm size.

Methods: We analyzed ascending aortic tissue from 58 TAA patients (28 bicuspid aortic valve [BAV], 30 tricuspid aortic valve [TAV]) and 8 healthy controls from heart transplantations (HTx). Unidirectional horizontal maximum tensile strength and elongation were measured at both inner (IC) and outer curvatures (OC) of the aortas. Quantitative real-time PCR assessed the expression of shear stress–associated markers (CRYAB, LRG1, INHBA), collagen, and elastin genes. Findings were correlated with TAA diameters from preoperative CT images. Gene expression was normalized to IC (set to 1). Tissue was provided by the institutional biobank.

Results: While maximum tensile strength was similar between OC and IC, maximum elongation was significantly reduced at the OC, both in BAV and TAV patients (46.76% vs. 76.03%, p < 0.001 and 42.37% vs. 50.68% p = 0.019, respectively). In all TAA patients, decreased tensile strength in both OC and IC correlated with increasing aortic diameter. Gene expression analysis revealed upregulation of LRG1 in OC for both groups (BAV: 2.72, p = 0.021; TAV: 1.95, p = 0.002) and downregulation of CRYAB in BAV OC (0.90, p = 0.038). Collagen genes showed significant changes, with COL11A1 upregulated in OC for both valve morphologies (BAV: 2.52; TAV: 2.58; both p < 0.001) and COL5A1 increased in BAV OC (1.84, p = 0.025). Notably, HTx controls exhibited no significant differences between OC and IC in gene expression or biomechanical properties.

Conclusion: Our findings demonstrate significantly increased stiffness and fragility of TAA tissue with elevated wall shear stress along the outer curvature, particularly in BAV patients. Reduced extensibility, altered shear stress–responsive gene expression, and collagen changes are all aspects involved in the pathophysiology of TAA, whereby their relative contribution as cause or otherwise response still have to be clarified. These results emphasize however the importance of a more sophisticated understanding of the interplay of molecular/genetic factors with biomechanical factors in TAA to allow for individualized risk stratification and thus treatment decision-making for patients.

Publication History

Article published online:
11 February 2025