The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Calcification by Valve Interstitial Cells Is Regulated by the Stiffness of the Extracellular Matrix
Abstract
Objective— Extensive remodeling of the valve ECM in calcific aortic valve sclerosis alters its mechanical properties, but little is known about the impact of matrix mechanics on the cells within the valve interstitium. In this study, the influence of matrix stiffness in modulating calcification by valve interstitial cells (VICs), and their differentiation to pathological phenotypes was assessed. Methods and Results— Primary porcine aortic VICs were cultured in standard media or calcifying media on constrained type I fibrillar collagen gels. Matrix stiffness was altered by changing only the thickness of the gels. Calcification did not occur in standard media, regardless of matrix stiffness. However, when VICs were grown in calcifying media on relatively compliant matrices with stiffness similar to that of normal tissue, they readily formed calcified aggregates of viable cells that expressed osteoblast-related transcripts and proteins. In contrast, VICs cultured in calcifying media on stiffer matrices (similar to stenotic tissue) differentiated to myofibroblasts and formed calcified aggregates that contained apoptotic cells. Actin depolymerization reduced aggregation on stiff, but not compliant, matrices. TGF-β1 potentiated aggregate formation on stiff matrices by enhancing α-smooth muscle actin expression and cellular contractility, but not on compliant matrices attributable to downregulation of TGF-β receptor I. Cell contraction by VICs inhibited Akt activation and enhanced apoptosis-dependent calcification on stiff matrices. Conclusions— Differentiation of VICs to pathological phenotypes in response to biochemical cues is modulated by matrix stiffness. Although osteogenic or myofibrogenic differentiation of VICs can result in calcification, the processes are distinct.
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Cites
Matrix elasticity directs stem cell lineage specification
Engler, A. J., Sen, S., Sweeney, H. L., & Discher, D. E. (2006) · Cell · doi:10.1016/j.cell.2006.06.044 · Cited by 13,915
Tissue Cells Feel and Respond to the Stiffness of Their Substrate
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Myofibroblasts and mechano-regulation of connective tissue remodelling
Tomasek, J. J., Gabbiani, G., Hinz, B., Chaponnier, C., & Brown, R. A. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm809 · Cited by 4,290
Clinical Factors Associated With Calcific Aortic Valve Disease
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Alpha-Smooth Muscle Actin Expression Upregulates Fibroblast Contractile Activity
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Bone Formation and Inflammation in Cardiac Valves
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Human Aortic Valve Calcification Is Associated With an Osteoblast Phenotype
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Cited by
Rajamannan, N. M., Evans, F. J., Aikawa, E., Grande-Allen, K. J., Demer, L. L., Heistad, D. D., Simmons, C. A., Masters, K. S., Mathieu, P., O'Brien, K. D., et al. (2011) · Circulation · doi:10.1161/circulationaha.110.006767 · Cited by 842
Self-citationEngineered In Vitro Disease Models
Benam, K. H., Dauth, S., Hassell, B., Herland, A., Jain, A., Jang, K.-J., Karalis, K., Kim, H. J., MacQueen, L., Mahmoodian, R., et al. (2015) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-012414-040418 · Cited by 554
Heart Valve Structure and Function in Development and Disease
Hinton, R. B., & Yutzey, K. E. (2011) · Annual Review of Physiology · doi:10.1146/annurev-physiol-012110-142145 · Cited by 498
Boning up on Wolff's Law: Mechanical regulation of the cells that make and maintain bone
Chen, J.-H., Liu, C., You, L., & Simmons, C. A. (2010) · Journal of Biomechanics · doi:10.1016/j.jbiomech.2009.09.016 · Cited by 422
Self-citationYutzey, K. E., Demer, L. L., Body, S. C., Huggins, G. S., Towler, D. A., Giachelli, C. M., Hofmann-Bowman, M. A., Mortlock, D. P., Rogers, M. B., Sadeghi, M. M., et al. (2014) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.114.302523 · Cited by 371
Metadata
- Authors
- Yip, C. Y. Y., Chen, J.-H., Zhao, R., & Simmons, C. A.
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2009-06
- Volume
- 29
- Issue
- 6
- Pages
- 936-942
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2139430471
- Cited by
- 329
- References
- 52
- FWCI
- 15.03
- Type
- journal article
- Language
- en
- Open access
- closed
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- Yip, C. Y. Y., Chen, J.-H., Zhao, R., & Simmons, C. A. (2009). Calcification by Valve Interstitial Cells Is Regulated by the Stiffness of the Extracellular Matrix. Arteriosclerosis, Thrombosis, and Vascular Biology. https://doi.org/10.1161/atvbaha.108.182394
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