Abstract
Introduction: Within the aortic valve leaflets (AVLs) reside a heterogeneous cell population holistically referred to as valve interstitial cells (VICs). These cells maintain the highly organized trilaminar extracellular matrix (ECM) structure in the AVL and are involved in the pathological progression of aortic valve disease (AVD). Various cell types have been reported in the AVL, including an understudied subpopulation of neurons. Since the mid-2000s, little has been done to report the possible role these neurons have in tissue homeostasis. Typically, imbedded sections of tissue chosen from specific areas of the valves are used to visualize immunoreactivity of these proteins. These sections usually come from the belly region or annular sections of the valve and seldom depict the entire leaflet anatomy. Hypothesis: Whole mount immunofluorescence microscopy allows us to map the 3D localization of these neuroendocrine markers throughout the entire aortic valve. Methods: Here, we gathered high resolution confocal microscopy images in whole mount mouse aortic valve tissues of various neuroendocrine markers such as tyrosine hydroxylase, protein gene product 9.5, and calcitonin gene related peptide. Results: We note that neuroendocrine markers mainly localize near the free edge on the ventricular surface of AVL tissue. We do not see the long dendritic neurons seen in the mitral and tricuspid valves, instead these markers are present in cells of varying morphologies throughout. Conclusions: The data gathered in this study aids our future efforts in determining mechanosensitive neural regulation of aortic valve leaflet mechanics and ECM remodeling. Future experiments will assess neuromodulation of valve rigidity under mechanical strain.
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