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Review
. 2011 May-Jun;20(3):168-76.
doi: 10.1016/j.carpath.2010.11.007. Epub 2011 Jan 22.

Bicuspid aortic valve disease: the role of oxidative stress in Lrp5 bone formation

Nalini M Rajamannan  1
Affiliations
Review

Bicuspid aortic valve disease: the role of oxidative stress in Lrp5 bone formation

Nalini M Rajamannan. Cardiovasc Pathol. 2011 May-Jun.

Abstract

The bicuspid aortic valve is a common congenital cardiac anomaly, having a prevalence of 0.9% to 1.37% in the general population and a male preponderance ratio of 2:1. The recognition of a bicuspid aortic valve is clinically relevant because of its association with aortic stenosis or regurgitation, aortic aneurysm or dissection, and infective endocarditis. Although some patients with a bicuspid aortic valve may go undetected without clinical complications for a lifetime, the vast majority will require intervention, most often surgery, at some point. In fact, the natural history of bicuspid aortic valve is that of valve calcification and progressive stenosis that typically occur at a faster rate than in tricuspid aortic valves. This pattern of presentation supports the hypothesis that shear stress in patients with congenitally abnormal aortic valves may contribute to an earlier leaflet calcification. However, there is emerging research data showing that the valve calcification process might have a similar pathophysiologic process to that of vascular atherosclerosis. This review focuses on the current knowledge of the cellular mechanisms of bicuspid aortic valve.

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Figures

Figure 1
Figure 1
Bicuspid Aortic Valve Removed from Surgical Valve Replacement demonstrating extensive calcification and bone present in the bicuspid valve removed at the time of surgical valve replacement. (Used with Permission from Wolters Kluwer Health, Publisher for Circulation.)
Figure 2
Figure 2
Photo demonstrates the bicuspid valve phenotype present in the subset of eNOS null mice found randomly in the mice by evaluating the valves in the eNOS null mice. (Used with Permission from Wolters Kluwer Health, Publisher for Circulation.)
Figure 3
Figure 3
The autosomal–dominant inheritance of the disease phenotype with complete penetrance of the Notch1 loss of function mutation. The Notch1 mutations segregate with the family members with aortic valve disease. There are also family members who expressed congenital heart abnormalities. (Used with Permission from Nature Publishing Group, Publisher for Nature.)
Figure 4
Figure 4
Bone immunohistochemistry for extracellular matrix and Lrp5/Notch1 signaling markers in Bicuspid Aortic Valves. PCNA- Proliferating nuclear cell antigen indicates upregulation of DNA polymerase during active proliferation. Alcian blue stains for cartilage which is minimal. The stain binds to proteoglycans. The Alizarin red is a stain for calcium and hydroxyapatite in the valves which was increased markedly in the valves. The Lrp5 and Wnt3a stain is localized in the myofibroblast cells which are differentiating to an osteoblast like phenotype. The Notch1 stain is much less than the canonical Wnt markers in the areas of complex bone formation. The Bone sialoprotein, Osteocalcin and Osteopontin stains are all upregulated in bicuspid tissues indicating osteogenic differentiation and later stage mineralization. (Used with Permission from Elsevier, Publisher for Journal of the American College of Cardiology.)
Figure 5
Figure 5
Proposed Cellular mechanisms of Bicuspid Aortic Valve Disease.
See this image and copyright information in PMC

References

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