Elevated cyclic stretch (15% and 20%) on porcine aortic valve cusps upregulated the expression of MMP-1, -2, -9 and cathepsin S and K, and increased cell proliferation and apoptosis at 20% stretch.
Does elevated cyclic stretch alter the expression and activity of proteolytic enzymes in aortic valve cusps?
Elevated mechanical stretch alters proteolytic enzyme expression in aortic valve cells, suggesting a mechanobiological pathway for degenerative aortic valve disease.
Matrix metalloproteinases (MMPs) and cathepsins are proteolytic enzymes that are upregulated in diseased aortic valve cusps. The objective of this study was to investigate whether elevated cyclic stretch causes an increased expression and activity of these proteolytic enzymes in the valve cusp. Circumferentially oriented fresh porcine aortic valve cusp sections were stretched to 10% (physiological), 15% (pathological), and 20% (hyperpathological) in a tensile stretch bioreactor for 24 and 48 h. The expression and activity of MMP-1, MMP-2, MMP-9, tissue inhibitor of MMP-1, and cathepsin L, S, and K were quantified and compared with fresh controls. Cell proliferation and apoptosis were also analyzed. As a result, at 10% physiological stretch, the expression and activity of remodeling enzymes were comparable with fresh controls. At 15% stretch, the expression of MMP-1, -2, -9 and cathepsin S and K were upregulated, whereas the expression of cathepsin L was downregulated compared with controls. A similar trend was observed at 20% stretch, but the magnitudes of upregulation and downregulation of the expression were less than those observed at 15%. In addition, there were significantly higher cell proliferation and apoptosis at 20% stretch compared with those of other treatment groups. In conclusion, elevated mechanical stretch on aortic valve cusps may detrimentally alter the proteolytic enzyme expression and activity in valve cells. This may trigger a cascade of events leading to an accelerated valve degeneration and disease progression.
Balachandran et al. (Sat,) conducted a other in Degenerative aortic valve disease. Elevated cyclic stretch (15% and 20%) vs. 10% physiological stretch and fresh controls was evaluated on Expression and activity of MMP-1, MMP-2, MMP-9, tissue inhibitor of MMP-1, and cathepsin L, S, and K, as well as cell proliferation and apoptosis. Elevated cyclic stretch (15% and 20%) on porcine aortic valve cusps upregulated the expression of MMP-1, -2, -9 and cathepsin S and K, and increased cell proliferation and apoptosis at 20% stretch.