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

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 medialintimal region R of BAV-ATAAs when compared with TAV-ATAAs (medial region N, amplitude of angular undulation of elastin = 10.67 degrees +/- 1.35 degrees vs 15.58 degrees +/- 1.91 degrees; P = .041; medial-intimal region R, amplitude of angular undulation of elastin = 9.8 degrees +/- 0.83 degrees vs 14.72 degrees +/- 1.64 degrees; 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 degrees +/- 0.95 degrees vs 14.56 degrees +/- 1.37 degrees; 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 aneurysmgeometries and aortic wall integrities in ATAAs arising in these different valve morphologies.