Abstract
The aortic valve (AoV) maintains unidirectional blood distribution from the left ventricle of the heart to the aorta for systemic circulation. The AoV leaflets rely on a precise extracellular matrix microarchitecture of collagen, elastin, and proteoglycans for appropriate biomechanical performance. We have previously demonstrated a relationship between the presence of pigment in the mouse AoV with elastic fiber patterning using multiphoton imaging. Here, we extended those findings using wholemount confocal microscopy revealing that elastic fibers were diminished in the AoV of hypopigmented mice (KitWv and albino) and were disorganized in the AoV of K5-Edn3 transgenic hyperpigmented mice when compared to wild type C57BL/6J mice. We further used atomic force microscopy to measure stiffness differences in the wholemount AoV leaflets of mice with different levels of pigmentation. We show that AoV leaflets of K5-Edn3 had overall higher stiffness (4.42 ± 0.35 kPa) when compared to those from KitWv (2.22 ± 0.21 kPa), albino (2.45 ± 0.16 kPa), and C57BL/6J (3.0 ± 0.16 kPa) mice. Despite the striking elastic fiber phenotype and noted stiffness differences, adult mutant mice were found to have no overt cardiac differences as measured by echocardiography. Our results indicate that pigmentation, but not melanocytes, is required for proper elastic fiber organization in the mouse AoV and dictates its biomechanical properties.
Highlights
The aortic valve (AoV) functions to maintain unidirectional blood flow between the left ventricle and the aorta for the systemic distribution
We further show the biomechanical properties in the mouse models using atomic force microscopy (AFM) in freshly dissected wholemount AoV leaflets
This is the first study to report the relationship of extracellular matrix (ECM) patterning and its associated biomechanical properties in freshly dissected wholemount AoV leaflets
Summary
The aortic valve (AoV) functions to maintain unidirectional blood flow between the left ventricle and the aorta for the systemic distribution. The AoV undergoes constant pressure, stress, flexure, biaxial tension, and compression during a cardiac cycle, which requires the AoV to be durable for ∼3 × 109 cardiac cycles over the course of an average lifetime. The AoV is composed of highly structured cellular and extracellular matrix (ECM) components required to maintain appropriate biomechanics. The AoV ECM is mainly composed of collagen, elastin, and proteoglycans. In the AoV, radially aligned elastic fibers and circumferentially aligned collagen fibers dictate AoV function [1]. Pathological alterations in alignment and composition compromise AoV biomechanics.
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