In vitro 3D model and miRNA drug delivery to target calcific aortic valve disease
Name
nihms861757.pdf
Description
Accepted version
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723.37 KB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
van der Ven, Casper FT
Wu, Pin-Jou
Tibbitt, Mark W
van Mil, Alain
Sluijter, Joost PG
Langer, Robert
Aikawa, Elena
Date Issued
2017
Journal
Clinical Science
Publisher
Portland Press Ltd.
Citation
van der Ven, C. F., et al. "In Vitro 3d Model and Mirna Drug Delivery to Target Calcific Aortic Valve Disease." Clin Sci (Lond) 131 3 (2017): 181-95.
Version
Author's final manuscript
Abstract
© 2017 The Author(s). Calcific aortic valve disease (CAVD) is the most prevalent valvular heart disease in the Western population, claiming 17000 deaths per year in the United States and affecting 25% of people older than 65 years of age. Contrary to traditional belief, CAVD is not a passive, degenerative disease but rather a dynamic disease, where initial cellular changes in the valve leaflets progress into fibrotic lesions that induce valve thickening and calcification. Advanced thickening and calcification impair valve function and lead to aortic stenosis (AS). Without intervention, progressive ventricular hypertrophy ensues, which ultimately results in heart failure and death. Currently, aortic valve replacement (AVR), surgical or transcatheter, is the only effective therapy to treat CAVD. However, these costly interventions are often delayed until the late stages of the disease. Nonetheless, 275000 are performed per year worldwide, and this is expected to triple by 2050. Given the current landscape, next-generation therapies for CAVD are needed to improve patient outcome and quality of life. Here, we first provide a background on the aortic valve (AV) and the pathobiology of CAVD as well as highlight current directions and future outlook on the development of functional 3D models of CAVD in vitro. We then consider an often-overlooked aspect contributing to CAVD: miRNA (mis)regulation. Therapeutics could potentially normalize miRNA levels in the early stages of the disease and may slow its progression or even reverse calcification. We close with a discussion of strategies that would enable the use of miRNA as a therapeutic for CAVD. This focuses on an overview of controlled delivery technologies for nucleic acid therapeutics to the valve or other target tissues.
MIT Department
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Chemical Engineering
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DOI of Published Version
https://doi.org/10.1042/CS20160378
