In vitro 3D model and miRNA drug delivery to target calcificaortic valve disease
发表状态：
Clin Sci (Lond). February 01; 131(3): 181–195
研究团队：
Casper F.T. van der Ven*,†,‡, Pin-Jou Wu§, Mark W. Tibbitt†, Alain van Mil‡,‖,¶, Joost P.G.Sluijter‡,‖,¶, Robert Langer†,**, and Elena Aikawa*,§
研究内容：
文章首先介绍了主动脉瓣(AV)和腔静脉疾病的病理生物学背景，并重点介绍了腔静脉疾病体外功能三维模型的发展方向和未来展望。然后，针对一个有助于CAVD经常被忽视的方面: miRNA (mis)调控。治疗可能在疾病早期使miRNA水平正常化，并可能减缓其进展，甚至逆转钙化。最后，将讨论能够将miRNA用于治疗CAVD的策略。本篇文章主要介绍核酸疗法在瓣膜或其他靶组织中的受控传递技术。
Abstract：
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 andcalcification 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 by2050. 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.
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