Related Experiment Video
Updated: Sep 10, 2025
07:31
Isolation of Human Primary Valve Cells for In vitro Disease Modeling
Published on: April 16, 2021
2.8K
Plasma-Derived Extracellular Vesicle-Propagated microRNA From Aortic Stenosis Patients Render Pro-Calcifying Effects
Avinash B Khandagale1, Padraic Corcoran2, Yuzhen Dan3
1Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.
JACC. Basic to Translational Science
|August 20, 2025
Summary
Extracellular vesicles (EVs) from aortic valve stenosis (AS) patients carry microRNAs (miRs) that promote valve calcification. Specific miRs, like miR-455-3p and miR-103a-3p, are key drivers of this process in VICs.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Biomaterials Science
Background:
- Aortic valve stenosis (AS) involves altered extracellular vesicle (EV) and microRNA (miR) expression.
- Understanding the role of EVs and miRs in AS pathogenesis is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the expression profiles of miRs within circulating EVs in severe AS patients.
- To determine the functional impact of AS-derived EVs and specific miRs on valvular interstitial cell (VIC) osteogenic differentiation and calcification.
Main Methods:
- Profiling of miR expression in circulating EVs from severe AS patients and healthy controls.
- In vitro experiments using EVs from AS patients to assess their effect on VICs.
- Analysis of pro-osteogenic gene and protein expression (osteocalcin, osteopontin) in VICs.
- Correlation analysis of specific miR expression levels (miR-455-3p, miR-103a-3p) with VIC calcification.
- Investigating the impact of miR alterations on VIC osteogenic differentiation and the expression of BMP4 and RUNX2.
Main Results:
- Several miRs were found to be differentially expressed in EVs from AS patients compared to controls.
- EVs from AS patients induced calcification in VICs by upregulating pro-osteogenic genes (osteocalcin, osteopontin).
- Expression levels of miR-455-3p and miR-103a-3p correlated with VIC calcification.
- Modulation of these miRs affected osteogenic differentiation of VICs and altered BMP4 and RUNX2 expression.
Conclusions:
- Circulating EVs carry miRs that contribute to the osteogenic process and calcification in AS.
- miR-455-3p and miR-103a-3p are significant players in AS-associated VIC calcification.
- Targeting these specific miRs or EVs may offer novel therapeutic strategies for aortic valve stenosis.
Keywords:
aortic valve stenosiscalcified valveextracellular vesiclesmicroRNAtranscatheter aortic valve replacementvalve interstitial cellsMore Related Videos
Related Concept Videos
01:22Mitral Stenosis I: Introduction
34
Mitral Valve Stenosis (MVS) is a heart condition where the mitral valve narrows, impeding blood circulation from the left atrium to the left ventricle. The etiology and pathophysiology of this condition are multifaceted, leading to a cascade of cardiovascular complications.Causes of Mitral Valve StenosisRheumatic Heart Disease: It is the main cause of mitral valve stenosis, particularly in developing nations. This condition arises from rheumatic fever, an inflammatory illness resulting from...
34
01:27Mitral Valve Prolapse I: Introduction
42
IntroductionThe mitral valve, one of the heart's four valves, regulates blood flow. These valves have flaps that open and close to direct blood properly through the heart and body. During each heartbeat, the flaps open for blood to pass through and seal shut to prevent backflow. Specifically, the mitral valve opens to allow blood flow from the heart's upper left chamber to the lower left chamber. It then closes securely as the lower left chamber contracts to pump blood to the body, preventing...
42