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Pigmentation Affects Elastic Fiber Patterning and Biomechanical Behavior of the Murine Aortic Valve

Sana Nasim, Popular Pandey, Rosemerie M. Kanashiro-Takeuchi, Jin He, Joshua D. Hutcheson, and Lisi Kos recently published a paper looking at the relationship between aortic valve pigmentation and elasticity, building on their previously-published work. Their full manuscript is publicly available in Frontiers in Cardiovascular Medicine. Here, we summarize their findings.

Sana Nasim, Popular Pandey, Rosemerie M. Kanashiro-Takeuchi, Jin He, Joshua D. Hutcheson, and Lisi Kos recently published a paper looking at the relationship between aortic valve pigmentation and elasticity, building on their previously-published work. Their full manuscript is publicly available in Frontiers in Cardiovascular Medicine. Here, we summarize their findings.

The aortic valve is necessary for unidirectional blood flow from the left ventricle to the aorta. Over the course of an average lifetime the aortic valve must open around a billion times – during a billion cardiac cycles. Elastic fibers in the valve leaflets make this possible. When properly aligned, these elastic fibers allow the valve leaflets to extend (to open the valve) and contract (to close the valve). Elastic fibers also maintain proper tension on the valve, ensuring that blood cannot flow into the aorta before the left ventricle is filled.

When these elastic fibers are not properly aligned, the valve does not function properly and blood flow can be dramatically disrupted. Abnormalities in aortic valve elasticity result in life-threatening congenital aortic valve defects and disease. Because the function of these elastic fibers is so critical to the function of the aortic valve, and therefore the heart, it is important to understand how they interact and function.

In mice, researchers have observed that there is more pigmentation within stiffer aortic valve leaflets and less pigmentation within more elastic leaflets. This suggests that pigment, the process of pigment production, or the pigment-producing cells themselves, called melanocytes, may play a role in the organization of elastic fibers within valve leaflets.

Nasim et al.’s past work has corroborated those findings. In an earlier 2021 paper, they compared mice with normal aortic valve pigmentation to mice with hyperpigmentation and mice with hypopigmentation. They found that mice with excessive pigmentation had many disorganized fibers, and that mice lacking pigmentation had very few elastic fibers, compared to normal (wild-type) mice. In essence, this is a goldilocks story – their results suggest that the presence of melanocytes and/or the pigments they produce must be just right in order for elastic fibers to exist and function properly.

The goal of Nasim et al.’s more recent study was to further investigate the correlation between aortic valve pigmentation and leaflet elasticity, and to determine whether it is melanocytes or just the pigments they produce that are linked to elasticity.

Using their previously-studies mouse models and this time including albino mice in their comparisons, Nasim et al. again found that mice with excessive pigmentation had many but disorganized fibers and that mice lacking both melanocytes and pigmentation had very few elastic fibers compared to normal (wild-type) mice. Importantly, albino mice have melanocytes but no pigmentation. Aortic valves from these mice had few elastic fibers; they looked similar to mice lacking both melanocytes and pigmentation. This suggests that pigmentation or pigment production – not just the presence of melanocytes – is linked to elasticity of the valve.