Editors' ChoiceAortic Valve Disease

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Science Translational Medicine  21 Dec 2011:
Vol. 3, Issue 114, pp. 114ec206
DOI: 10.1126/scitranslmed.3003581

Aortic stenosis (narrowing of the aortic valve in the heart) is a disease of aging that results from tissue remodeling gone awry. Ossification—in which new bone tissue is deposited in the aortic valve—is a known but poorly understood phenomenon that was thought to be due to local tissue degeneration of the aortic valve. Now, work by Egan et al. suggests that bone marrow–derived circulating osteogenic precursor cells are involved in the process.

In previous work, the researchers showed that circulating osteogenic precursor cells are present in preosseous lesions in humans and can produce extraskeletal bone in mice, suggesting that such cells might play a role in aortic stenosis. To investigate this possibility, Egan et al. examined heart valves that had been removed from patients with aortic valve disease during cardiac valve replacement surgery. Of the 105 valves studied histologically, 13 displayed signs of heterotopic bone formation. Multiple stages of ossification, including infiltration of inflammatory cells, fibroproliferation, neovascularity, and the appearance of cartilage and bone, were detected. Mature bone was represented by the presence of osteocytes and bone-lining cells. Circulating osteogenic precursor cells, identified by coexpression of the osteogenic marker type 1 collagen and the hematopoietic marker CD45, were found in areas of early bone formation. Comparison of tissue from the same individual demonstrated that regions of valvular tissue with bone formation had significantly more circulating osteogneic precursors cells than regions without bone formation.

These findings suggest that circulating osteogenic precursor cells are attracted to areas of inflammation and injury on the aortic valve and subsequently promote ossification. Potentially, these cells represent a key component of the pathogenesis of calcific aortic valve disease that may serve as an important target for future cellular therapies.

K. P. Egan et al., Role for circulating osteogenic precursor cells in aortic valvular disease. Arterioscler. Thromb. Vasc. Biol. 31, 2965–2971 (2011). [Abstract]

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