Letter: Blinking valve.

Biologically derived, chemically modified collagenous tissues are being increasingly used to fabricate cardiac valve prostheses and as biomaterials in cardiovascular repair. A stress-free state during chemical modification has been shown to preserve the collagen fiber architecture of the native tissue, potentially preserving native mechanical properties and improving prostheses durability. However, it is not known if the native collagen fiber architecture is stable during long-term in vivo operation. To address this question, we obtained porcine aortic valves chemically treated at (i) 0 mmHg transvalvular pressure (with 40 mmHg aortic pressure) and (ii) 4 mmHg transvalvular pressure, then subjected the valves to 0, 1 x 10(6), 50 x 10(6), and 200 x 10(6) in vitro accelerated wear testing (AWT) cycles. The resulting changes in collagen fiber architecture were quantified using small angle light scattering analysis (SALS). SALS measurements indicated that collagen fibers in the 0 mmHg pressure-fixed leaflets became more aligned between 1 x 10(6) and 50 x 10(6) AWT cycles. In contrast, only minor changes (not statistically significant) in collagen fiber orientation occurred in the 4 mmHg pressure-fixed valvular tissue with cycling. It was also noted that although the 0 mmHg group was fixed without transvalvular pressure, distention of the root induced significant changes in collagen structure of the leaflets. Overall, our observations suggest that the native collagen fiber crimp of the 0 mmHg pressure-fixed leaflets were rapidly lost after only 50 x 10(6) AWT cycles (equivalent to approximately 1.6 patient years) and thus may not be maintained over a sufficient period of time to be clinically beneficial. Further, the collagen structure of the native aortic valve is exquisitely sensitive to dimensional change in the aortic root-independent of the presence of transvalvular pressure. Our findings also suggest that without in vivo remodeling, any collagenous tissue used to fabricate BHV may undergo similar degenerative, irreversible changes in vivo.

Aortic Valve↗

PubMed2005

Influence of receptor activator of nuclear factor kappa B on human aortic valve myofibroblasts.

Calcific aortic valve stenosis, the main heart valve disease in the elderly, is based on progressive calcification and fibrous thickening of the valve. Several reports addressed the pathogenesis of tissue calcification in this disorder, but few data exist on the molecular mechanisms of the fibrosis and remodeling of the extracellular matrix. The cytokine "receptor activator of nuclear factor kappa B ligand" (RANKL), is expressed in stenotic aortic valves and involved in valvular calcification during calcific aortic valve stenosis. The present study aimed to assess the influence of RANKL on the molecular mechanisms of connective tissue remodeling. In an established cell culture model of primary human aortic valve myofibroblasts, stimulation with RANKL increased cell proliferation as compared to medium alone. Matrix metalloproteinase (MMP)-1 was detectable time-dependently in conditioned media from RANKL-stimulated cells, but absent in media from control cells. MMP-1 activity was increased by RANKL, as measured by collagenase activity assay. Zymography showed an increase in active MMP-2 in RANKL-stimulated cells. These results support the concept that MMPs are involved in the connective tissue remodeling during calcific aortic valve stenosis. RANKL might regulate this process by promoting cell proliferation and MMP expression and activation.

Aortic Valve↗