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Smooth muscle cells (SMCs) usually express a contractile phenotype in the healthy aorta. However, aortic SMCs have the ability to undergo profound changes in phenotype in response to changes in their extracellular environment, as occurs in ascending thoracic aortic aneurysms (ATAA). Accordingly, there is a pressing need to quantify the mechanobiological effects of these changes at single cell level. To address this need, we applied Traction Force Microscopy (TFM) on 759 cells coming from three primary healthy (AoPrim) human SMC lineages and three primary aneurysmal (AnevPrim) human SMC lineages, from age and gender matched donors. We measured the basal traction forces applied by each of these cells onto compliant hydrogels of different stiffness (4, 8, 12, 25 kPa). Although the range of force generation by SMCs suggested some heterogeneity, we observed that: 1. the traction forces were significantly larger on substrates of larger stiffness; 2. traction forces in AnevPrim were significantly higher than in AoPrim cells. We modelled computationally the dynamic force generation process in SMCs using the motor-clutch model and found that it accounts well for the stiffness-dependent traction forces. The existence of larger traction forces in the AnevPrim SMCs were related to the larger size of cells in these lineages. We conclude that phenotype changes occurring in ATAA, which were previously known to reduce the expression of elongated and contractile SMCs (rendering SMCs less responsive to vasoactive agents), tend also to induce stronger SMCs. Future work aims at understanding the causes of this alteration process in aortic aneurysms. [ABSTRACT FROM AUTHOR]

Background: Ascending thoracic aortic aneurysm (ATAA) predisposes patients to aortic dissection and has been associated with diminished tensile strength and disruption of collagen. Ascending thoracic aortic aneurysms arising in patients with bicuspid aortic valve (BAV) develop earlier than in those with tricuspid aortic valves (TAV) and have a different risk of dissection. The purpose of this study was to compare aortic wall tensile strength between BAV and TAV ATAAs and determine whether the collagen content of the ATAA wall is associated with tensile strength and valve phenotype. Methods: Longitudinally and circumferentially oriented strips of ATAA tissue obtained during elective surgery were stretched to failure, and collagen content was estimated by hydroxyproline assay. Experimental stress-strain data were analyzed for failure strength and elastic mechanical variables: α, β, and maximal tangential stiffness. Results: The circumferential and longitudinal tensile strengths were higher for BAV ATAAs when compared with TAV ATAAs. The α and β were lower for BAV ATAAs when compared with TAV ATAAs. The maximal tangential stiffness was higher for circumferential when compared with longitudinal orientation in both BAV and TAV ATAAs. The amount of hydroxyproline was equivalent in BAV and TAV ATAA specimens. Although there was a moderate correlation between the collagen content and tensile strength for TAV, this correlation is not present in BAV. Conclusions: The increased tensile strength and decreased values of α and β in BAV ATAAs despite uniform collagen content between groups indicate that microstructural changes in collagen contribute to BAV-associated aortopathy. [Copyright &y& Elsevier]

In order to prevent the occurrence of aortic adverse events in ascending thoracic aortic aneurysm patients, preventive surgery is the sole option in case of large aneurysm. Identifying high-risk patients timely and accurately requires effective predictive indicators of aortic adverse events and accurate risk stratification thresholds. Absolute diameter measured after a single imaging examination, which has been used as the predictive indicator for decades, has been proved to be ineffective for risk stratification in moderately dilated aorta. Previously, new indicators combining absolute diameters with personalized parameters have been reported to show better predictive power of aortic adverse events than absolute diameters by correcting the effect of these parameters on the diameters. Meanwhile, combining three-dimensional parameters to formulate risk stratification thresholds not only may characterize the aortic risk morphology more precisely, but also predict aortic adverse events more accurately. These new indicators may provide more systematic assessment methods of patients' risk, formulate more personalized intervention strategies for ascending thoracic aortic aneurysm patients, and also provide a basis for researchers to develop more accurate and effective risk thresholds. We also highlight that the algorithm obtained by combining multiple indicators may be a better choice compared with single indicator, but this still requires the support of more evidence. Due to the particularity of syndromic aortic disease, whether these new indicators can be used for its risk stratification is still uncertain. Therefore, the scope of this manuscript does not include this kind of disease., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-2728). The authors have no conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)