Related Experiment Video
Updated: Mar 9, 2026
Isolation of Human Primary Valve Cells for In vitro Disease Modeling
Published on: April 16, 2021
In vitro 3D model and miRNA drug delivery to target calcific aortic valve disease
Casper F T van der Ven1,2,3, Pin-Jou Wu4, Mark W Tibbitt2
1Center for Excellence in Vascular Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, U.S.A.
Insights
Calcific aortic valve disease (CAVD) is a dynamic process, not just degeneration. MicroRNA (miRNA) dysregulation is a key factor, offering potential therapeutic targets for early intervention and treatment of aortic stenosis.
Area of Science:
- Cardiovascular Medicine
- Molecular Biology
- Biotechnology
Background:
- Calcific aortic valve disease (CAVD) is the most common valvular heart disease in Western populations, affecting 25% of individuals over 65.
- CAVD is a dynamic disease involving cellular changes, fibrosis, thickening, and calcification, leading to aortic stenosis (AS) and heart failure.
- Current treatments like aortic valve replacement (AVR) are often delayed and costly, highlighting the need for novel therapies.
Purpose of the Study:
- To provide a comprehensive overview of the aortic valve (AV) and CAVD pathobiology.
- To explore the role of microRNA (miRNA) dysregulation in CAVD.
- To discuss the potential of miRNA-based therapeutics and delivery technologies for CAVD.
Main Methods:
- Review of existing literature on CAVD pathobiology and current treatment strategies.
- Analysis of the role of miRNA (mis)regulation in the progression of CAVD.
- Discussion of in vitro 3D models for studying CAVD.
- Overview of controlled delivery technologies for nucleic acid therapeutics.
Main Results:
- CAVD is an active cellular disease, not merely degenerative.
- miRNA dysregulation is identified as a significant, yet often overlooked, contributor to CAVD.
- Development of functional 3D in vitro models is progressing.
Conclusions:
- miRNA-based therapeutics hold promise for normalizing miRNA levels in early-stage CAVD, potentially slowing or reversing calcification.
- Controlled delivery systems are crucial for the effective therapeutic application of miRNAs in CAVD.
- Next-generation therapies targeting miRNA dysregulation are needed to improve patient outcomes.
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 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.
