Abstract
An understanding of how mechanical forces impact cells within valve leaflets would greatly benefit the development of a tissue-engineered heart valve. In this study, the effect of constant ambient pressure on the biological properties of heart valve leaflets was evaluated using a custom-designed pressure system. Native porcine aortic valve leaflets were exposed to static pressures of 100, 140, or 170 mmHg for 48 h. Collagen synthesis, DNA synthesis, sulfated glycoaminoglycan (sGAG) synthesis, α–SMC actin expression, and extracellular matrix (ECM) structure were examined. Results showed that elevated pressure caused an increase in collagen synthesis. This increase was not statistically significant at 100 mmHg, but at 140 mmHg and 170 mmHg collagen synthesis increased by 37.5 and 90%, respectively. No significant difference in DNA or sGAG synthesis was observed at elevated pressures, with the exception that DNA synthesis at 100 mmHg decreased. A notable decline in α–SMC actin was observed over the course of the experiments although no significant difference was observed between the pressure and control groups. It was concluded that elevated pressure caused a proportional increase in collagen synthesis of porcine aortic valve leaflets, but was unable to preserve α-SMC actin immunoreactive cells.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
REFERENCES
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, 2002.
Garvey, W., A. Fathi, F. Bigelow, B. Carpenter, and C. Jimenez. Improved Movat pentachrome stain. Stain Technol. 61:60–62, 1986.
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.
Hishikawa, K., T. Nakaki, T. Marumo, M. Hayashi, H. Suzuki, R. Kato, and T. Saruta. Pressure promotes DNA synthesis in rat cultured vascular smooth muscle cells. J. Clin. Invest. 93:1975–1980, 1994.
Hishikawa, K., T. Nakaki, H. Suzuki, T. Saruta, and R. Kato. Transmural pressure inhibits nitric oxide release from human endothelial cells. Eur. J. Pharmacol. 215:329–331, 1992.
Hunter, C. J., S. M. Imler, P. Malaviya, R. M. Nerem, and M. E. Levenston. Mechanical compression alters gene expression and extracellular matrix synthesis by chondrocytes cultured in collagen I gels. Biomaterials 23:1249–1259, 2002.
Hutton, W. C., W. A. Elmer, S. D. Boden, S. Hyon, Y. Toribatake, K. Tomita, and G. A. Hair. The effect of hydrostatic pressure on intervertebral disc metabolism. Spine 24:1507–1515, 1999.
Katwa, L. C., S. C. Tyagi, S. E. Campbell, S. J. Lee, G. T. Cicila, and K. T. Weber. Valvular interstitial cells express angiotensinogen 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.
Palmoski, M. J., and K. D. Brandt. Effects of static and cyclic compressive loading on articular cartilage plugs in vitro. Arthritis Rheum. 27:675–681, 1984.
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 hypertension. II. [35S]sulfate incorporation into aorta proteoglycans of spontaneously hypertensive rats. Coll. Relat. Res. 6:103–120, 1986.
Roy, A., N. J. Brand, and M. H. Yacoub. Expression of 5-hydroxytryptamine receptor subtype messenger RNA in interstitial 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.
Salwen, S. A., D. H. Szarowski, J. N. Turner, and R. Bizios. Three-dimensional changes of the cytoskeleton of vascular endothelial cells exposed to sustained hydrostatic pressure. Med. Biol. Eng. Comput. 36:520–527, 1998.
Schmidt, A., J. Grunwald, and E. Buddecke E. [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.
Smith, R. L., S. F. Rusk, B. E. Ellison, P. Wessells, K. Tsuchiya, D. R. Carter, W. E. Caler, L. J. Sandell, and D. J. Schurman. In vitro stimulation of articular chondrocyte mRNA and extracellular matrix synthesis by hydrostatic pressure. J. Orthop. Res. 14:53–60, 1996.
Thubrikar, M. The Aortic Valve. Boca Raton, FL: CRC press, 1990, 112pp.
Tokunaga, O., and T. Watanabe. Properties of endothelial cell and smooth muscle cell cultured in ambient pressure. In Vitro Cell Dev. Biol. 23:528–534, 1987.
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 endothelial cell proliferation. J. Mol. Cell Cardiol. 30:609–615, 1998.
Willems, I. E., M. G. Havenith, J. F. Smits, and M. J. Daemen. Structural alterations in heart valves during left ventricular pressure overload in the rat. Lab. Invest. 71:127–133, 1994.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Xing, Y., He, Z., Warnock, J.N. et al. Effects of Constant Static Pressure on the Biological Properties of Porcine Aortic Valve Leaflets. Annals of Biomedical Engineering 32, 555–562 (2004). https://doi.org/10.1023/B:ABME.0000019175.12013.8f
Issue Date:
DOI: https://doi.org/10.1023/B:ABME.0000019175.12013.8f