Extracellular matrix fiber microarchitecture is region-specific in bicuspid aortic valve-associated ascending aortopathy

Abstract

Objective Ascending thoracic aortic aneurysm (ATAA) in patients with bicuspid aortic valve (BAV) commonly dilate asymmetrically compared with patients with tricuspid aortic valve (TAV). This discrepancy in aneurysm geometry led us to hypothesize that microarchitectural differences underlie the observed asymmetric dilatation pattern. The purpose of this study was to characterize the microarchitectural distinctions of the extracellular matrix of the 2 phenotypes with a focus on the proportion of radially oriented elastin and collagen fibers in different circumferential aortic regions. Methods Aortic tissue rings were obtained just distal to the sinotubular junction from patients with BAV or TAV undergoing elective aneurysm repair. They were sectioned into three circumferentially based regions according to adjacent aortic sinus segment (left coronary sinus [L], right coronary sinus [R], or noncoronary sinus [N]). Multiphoton microscopy was used to quantify and characterize the number of radially oriented elastin and collagen fibers. Results There were fewer radially oriented fibers in medial region N and medial-intimal region R of BAV-ATAAs when compared with TAV-ATAAs (medial region N, amplitude of angular undulation of elastin = 10.67° ± 1.35° vs 15.58° ± 1.91°; P = .041; medial-intimal region R, amplitude of angular undulation of elastin = 9.83° ± 0.83° vs 14.72° ± 1.64°; P = .015). Conversely, fibers became more radially oriented in the medial-intimal region L of BAV-ATAA when compared with TAV-ATAA (amplitude of angular undulation of collagen = 18.67° ± 0.95° vs 14.56° ± 1.37°; P = .041). Conclusions The differential pattern of fiber orientation noted between L and N-R regions help explain the unique pattern of greater curvature dilatation of BAV-ATAA. The distinctions noted in matrix microarchitecture may form the basis of differing aneurysm geometries and aortic wall integrities in ATAAs arising in these different valve morphologies.

Elevated oxidative stress in the aortic media of patients with bicuspid aortic valve

“…17–19 In addition, it is likely that all patients with BAV have a certain degree of ascending aortopathy because they do exhibit a greater ascending aortic diameter compared with TAV patients, 19–21 even when matched for variables such as sex, age, or degree or valvulopathy. 22 The distinct manifestations of BAV- versus TAV-associated aortopathy is further supported by our previous work at the tissue, cellular, and molecular levels showing distinct biomechanical properties associated with differences in extracellular matrix maturity and architecture 23–27 and altered SMC response to oxidative stress 6,28 in the BAV versus TAV aortopathy.…”

Aortic shear stress in patients with bicuspid aortic valve with stenosis and insufficiency

“…Meanwhile, BAV-AS patients who exhibit exaggerated flow eccentricity and elevation of regional WSS could benefit from less aggressive treatment strategies including reduction aortoplasty guided by WSS mapping. It was supported by long-term follow-up studies that clinical outcomes of reduction aortoplasty might rely on the extent of localized degeneration of the aortic wall at the greater curvature, 36, 37 which was typically associated with BAV stenosis. Considering the elder age of BAV-AS patients, the less aggressive approach of reduction aortoplasty could be a surgical option for future clinical studies since it was associated with lower rate of early postoperative complications as well as shorter ICU and hospital stay.…”

Aortic Valve Stenosis Alters Expression of Regional Aortic Wall Shear Stress: New Insights From a 4‐Dimensional Flow Magnetic Resonance Imaging Study of 571 Subjects

“…Recent work by Guzzardi et al has shown that regions of increased WSS, measured by 4D flow MRI in BAV patients before aortic valve repair, corresponded with extracellular matrix dysregulation and elastic fiber degeneration in resected tissue samples from the same patients 8. Tsamis et al found that BAV patients exhibit asymmetric dilatation of the greater curvature of the aorta, compared to symmetric dilatation in TAV patients, concomitant with different elastin and collagen fiber orientation between the types of valves 36. Additionally, Girdauskas et al recently determined that there was no difference in correlation patterns between functional aortic root parameters and expression of aortopathy between BAV and TAV patients with aortic dilatation and AS 9.…”

“…8 Tsamis et al found that BAV patients exhibit asymmetric dilatation of the greater curvature of the aorta, compared to symmetric dilatation in TAV patients, concomitant with different elastin and collagen fiber orientation between the types of valves. 36 Additionally, Girdauskas et al recently determined that there was no difference in correlation patterns between functional aortic root parameters and expression of aortopathy between BAV and TAV patients with aortic dilatation and AS. 9 The findings of our study indicate that these apparent contradictions may be brought about by the presence of AS, which can significantly alter and dominate aortic 3D WSS patterns irrespective of valve type.…”