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Updated: Jul 31, 2026
Isolation and Characterization of Primary Rat Valve Interstitial Cells: A New Model to Study Aortic Valve Calcification
Published on: November 20, 2017
Inhibition of lnc-COL6A1-6-Alleviated Osteogenic Differentiation of Valvular Interstitial Cells During Aortic Valve
Ying Gu1, Fan Yang2, Quangong Zhao3
1Department of Cardiology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu, China.
Insights
Long noncoding RNA COL6A1-6 (lnc-COL6A1-6) drives aortic valve calcification by promoting autophagy. Inhibiting lnc-COL6A1-6 reduces calcification and offers a potential therapeutic strategy for calcific aortic valve disease (CAVD).
Area of Science:
- Cardiovascular Biology
- Molecular Biology
- RNA Biology
Background:
- Calcific aortic valve disease (CAVD) is a widespread condition in elderly populations, characterized by aortic valve remodeling and calcification.
- Aberrant expression of long noncoding RNAs (lncRNAs) is implicated in the pathogenesis of various diseases, including CAVD.
Purpose of the Study:
- To identify key lncRNAs involved in CAVD pathogenesis.
- To elucidate the role of lnc-COL6A1-6 in valvular interstitial cell (VIC) calcification.
- To investigate the underlying molecular mechanisms, including miRNA-mRNA interactions and autophagy.
Main Methods:
- Differential expression analysis of lncRNAs in calcified aortic valve tissues.
- Monitoring lncRNA expression during VIC calcification.
- Functional studies involving lnc-COL6A1-6 inhibition in VICs.
- Bioinformatic prediction of miRNA-mRNA regulatory networks.
- Assessment of autophagy markers and autophagic flux.
- Pharmacological inhibition of autophagy.
Main Results:
- 241 differentially expressed lncRNAs were identified, with lnc-COL6A1-6 showing significantly increased expression in calcified VICs.
- Inhibition of lnc-COL6A1-6 reduced VIC calcification, calcium deposition, and expression of key calcification markers (Runx2, OPN).
- lnc-COL6A1-6 was predicted to regulate numerous genes via a miRNA-mRNA network, with top targets enriched in autophagy pathways.
- lnc-COL6A1-6 knockdown attenuated autophagic flux in VICs, and autophagy inhibition abolished the anti-calcific effects of lnc-COL6A1-6 knockdown.
Conclusions:
- lnc-COL6A1-6 plays a critical role in promoting VIC calcification through a miRNA-mRNA regulatory network that enhances autophagic activity.
- lnc-COL6A1-6 represents a potential therapeutic target for CAVD, with its inhibition offering a strategy to mitigate valve calcification by reducing autophagy.
Abstract:
Background: Calcific aortic valve disease (CAVD) is a prevalent valvular heart disease characterized by the fibrocalcific remodeling of the aortic valves, leading to significant health issues among the elderly population worldwide. The aberrant expression of long noncoding RNAs (lncRNAs) is closely associated with the pathogenesis of various diseases. Methods and Results: A total of 241 differentially expressed lncRNAs were identified in calcified aortic valve tissues (fold change of ≥ 2 and p value < 0.05), including 65 upregulated and 176 downregulated lncRNAs. The expression of the Top 5 upregulated lncRNAs was monitored during the calcification of valvular interstitial cell (VIC). Notably, the expression of lnc-PRDM8-3 and lnc-COL6A1-6 in VICs increased significantly after calcification induction and was sustained at high levels. Inhibition of lnc-COL6A1-6, but not lnc-PRDM8-3, obviously alleviated the calcification of VICs, as evidenced by a marked reduction in calcium deposition, decreased alkaline phosphatase activity, and downregulated expression of Runx2 and OPN. Bioinformatic analysis predicted that lnc-COL6A1-6 might serve as a competing endogenous RNA for 11 miRNAs, potentially regulating the expression of 784 target genes. Among these, the Top 50 target genes were found to be significantly enriched in autophagy-related biological processes. Consistently, elevated levels of the autophagic markers Beclin 1 and LC3β were detected in calcified aortic valve tissues. Inhibition of lnc-COL6A1-6 significantly reduced autophagic flux in VICs under calcification-inducing conditions. Importantly, pharmacological inhibition of autophagy using chloroquine abolished the anticalcific effects of lnc-COL6A1-6 knockdown. Conclusions: The present study identified a lnc-COL6A1-6-mediated miRNA-mRNA regulatory network in aortic valve calcification. Knockdown of lnc-COL6A1-6 could mitigate VIC calcification by attenuating autophagic activity, highlighting its potential as a therapeutic target for CAVD.
