Abstract
An understanding of how mechanical forces impact cells within valve leaflets would greatly benefit the development of a tissue-engineered heart valve. Previous studies by this group have shown that exposure to constant static pressure leads to enhanced collagen synthesis in porcine aortic valve leaflets. In this study, the effect of cyclic pressure was evaluated using a custom-designed pressure system. Different pressure magnitudes (100, 140, and 170 mmHg) as well as pulse frequencies (0.5, 1.167, and 2 Hz) were studied. Collagen synthesis, cell proliferation, sGAG synthesis, α-SMC actin expression, and extracellular matrix (ECM) structure were chosen as markers for valvular biological responses. Results showed that aortic valve leaflets responded to cyclic pressure in a magnitude and frequency-dependent manner. Increases in pressure magnitude (with the frequency fixed at 1.167 Hz) resulted in significant increases in both collagen and sGAG synthesis, while DNA synthesis remained unchanged. Responses to pulse frequency (with the magnitude fixed at 100 mmHg) were more complex. Collagen and sGAG synthesis were increased by 25 and 14% respectively at 0.5 Hz; but were not affected at 1.167 and 2 Hz. In contrast, DNA synthesis increased by 72% at 2 Hz, but not at 0.5 and 1.167 Hz. Under extreme pressure conditions (170 mmHg, 2 Hz), collagen and sGAG synthesis were increased but to a lesser degree than at 170 mmHg, and 1.167 Hz. Cell proliferation was not affected. A notable decline in α-SMC actin was observed over the course of the experiments, although no significant difference was observed between the cyclic pressure and control groups. It was concluded that cyclic pressure affected biosynthetic activity of aortic valve leaflets in a magnitude and frequency dependent manner. Collagen and sGAG synthesis were positively correlated and more responsive to pressure magnitude than pulse frequency. DNA synthesis was more responsive to pulse frequency than pressure magnitude. However, when combined, pressure magnitude and pulse frequency appeared to have an attenuating effect on each other. The number of α-SMC actin positive cells did not vary with cyclic pressure, regardless of pulse frequency and pressure magnitude.
Similar content being viewed by others
REFERENCES
Chesler, N. C., D. N. Ku, and Z. S. Galis. Transmural pressure induces matrix-degrading activity in porcine arteries ex vivo. Am. J. Physiol. 277 (Heart Circ. Physiol. 46): H2002–H2009, 1999.
Dreger, S. A., P. M. Taylor, S. P. Allen, and M. H. Yacoub. Profile and localization of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in human heart valves. J. Heart Valve Dis. 11: 875–880, 2003.
Hafizi, S., P. M. Taylor, A. H. Chester, S. P. Allen, and M. H. Yacoub. Mitogenic and secretory responses of human valve interstitial cells to vasoactive agents. J. Heart Valve Dis. 9:454–458, 2000.
Hunter, C. J., S. M. Imler, P. Malaviya, R. M. Nerem, and M. E. Levenston. Mechanical compression alters gene expres-sion and extracellular matrix synthesis by chondrocytes cultured in collagen I gels. Biomaterials. 23:1249–1259, 2002.
Kaspar D., W. Seidl, C. Neidlinger-Wilke, A. Beck, L. Claes, and A. Ignatius. Proliferation of human-derived osteoblast-like cells depends on the cycle number and frequency of uniaxial strain. J. Biomech. 35(7): 873–880, 2002.
Katwa, L. C., S. C. Tyagi, S. E. Campbell, S. J. Lee, G. T. Cicila, and K. T. Weber. Valvular interstitial cells express angiotensino-gen and cathepsin D, and generate angiotensin peptides. Int. J. Biochem. Cell Biol. 28:807–821, 1996.
Lipke, D. W., and J. R. Couchman. Increased proteoglycan synthesis by the cardiovascular system of coarctation hypertensive rats. J. Cell Physiol. 147:479–486, 1991.
Nagatomi J., B. P. Arulanandam, D. W. Metzger, A. Meunier, and R. Bizios, Frequency-and duration-dependent effects of cyclic pressure on select bone cell functions. Tissue Eng. 7(6): 717–28, 2001.
Quick, D. W., K. S. Kunzelman, J. M. Kneebone, and R. P. Cochran. Collagen synthesis is upregulated in mitral valves subjected to altered stress. ASAIO J. 43:181–186, 1997.
Rabkin, E., M. Aikawa, J. R. Stone, Y. Fukumoto, P. Libby, and F. J. Schoen. Activated interstitial myofibroblasts express catabolic enzymes and mediate matrix remodeling in myxomatous heart valves. Circulation 104:2525–2532, 2001.
Reynertson, R. H., and L. Roden. Proteoglycans and hyperten-sion. II. [ 35 S] sulfate incorporation into aorta proteoglycans of spontaneously hypertensive rats. Coll. Relat. Res. 6:103–120, 1986.
Roelofsen, J., J. Klein-Nulend, and E. H. Burger. Mechanical stimulation by intermittent hydrostatic compression promotes bone-specific gene expression in vitro. J. Biomech. 28(12): 1493–1503, 1995.
Roy, A., N. J. Brand, and M. H. Yacoub, Expression of 5-hydroxytryptamine receptor subtype messenger RNA in inter-stitial cells from human heart valves. J. Heart Valve Dis. 9:256–260, 2000.
Roy, A., N. J. Brand, and M. H. Yacoub. Molecular characterization of interstitial cells isolated from human heart valves. J. Heart Valve Dis. 9:459–464, 2000.
Schmidt, A., J. Grunwald, and E. Buddecke. [35S] proteoglycan metabolism of arterial smooth muscle cells cultured from normotensive and hypertensive rats. Atherosclerosis 45:299–310, 1982.
Schneider, P. J., and J. D. Deck. Tissue and cell renewal in the natural aortic valve of rats: an autoradiographic study. Cardiovasc. Res. 15:181–189, 1981.
Shin, H. Y., R. Bizios, and M. E. Garritsen. Cyclic pressure modeulates endothelial barrier function. Endothelium 10(3):170–187, 2003.
Shin H. Y., M. E. Gerritsen, and R. Bizios. Regulation of endothelial cell proliferation and apoptosis by cyclic pressure. Ann. Biomed. Eng. 30(3): 297–304, 2002.
Tanaka, S. M., J. Li, R. L. Duncan, H. Yokota, D. B. Burr, and C. H. Turner. Effects of broad frequency vibration on cultured osteoblasts. J. Biomech. 36(1): 73–80, 2003.
Thubrikar, M.The Aortic Valve, Boca Raton, FL: CRC Press, 1990, p. 112.
Vouyouka, A. G., R. J. Powell, J. Ricotta, H. Chen, D. J. Dudrick, C. J. Sawmiller, S. J. Dudrick, and B. E. Sumpio. Ambient pulsatile pressure modulates endothe-lial cell proliferation. J. Mol. Cell Cardiol. 30:609–615, 1998.
Weber, K. T., Y. Sun, L. C. Katwa, J. P. Cleutjens, and G. Zhou. Connective tissue and repair in the heart. Poten-tial regulatory mechanisms. Ann. N.Y. Acad. Sci. 752:286–299, 1995.
Willems, I. E., M. G. Havenith, J. F. Smits, and M. J. Daemen. Structural alterations in heart valves during left ventricu-lar pressure overload in the rat. Lab. Invest. 71:127–133, 1994.
Wong M., M. Siegrist, and K. Goodwin. Cyclic tensile strain and cyclic hrdrostatic pressure differentially regulate expression of hypertrophic markers in primary chondrocytes. Bone 33(4):685–693, 2003.
Xing, Y., Z. He, J. N. Warnock, S. L. Hilbert, and A. P. Yoganathan. Effects of constant static pressure on the bio-logical properties of porcine aortic valve leaflets. Ann. Biomed. Eng. 32(4):555–562, 2004.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Xing, Y., Warnock, J.N., He, Z. et al. Cyclic Pressure Affects the Biological Properties of Porcine Aortic Valve Leaflets in a Magnitude and Frequency Dependent Manner. Annals of Biomedical Engineering 32, 1461–1470 (2004). https://doi.org/10.1114/B:ABME.0000049031.07512.11
Issue Date:
DOI: https://doi.org/10.1114/B:ABME.0000049031.07512.11