ArticleJCI insight2022
Increased Ca2+ influx through CaV1.2 drives aortic valve calcification.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- ALOX5-Mediated LTA4 Production Enhances PLCG2/IP3 Signaling and Exacerbates Calcification in Human Aortic Valve Interstitial Cells.Acta Cardiologica Sinica · 2026Article
- Voltage-Dependent Ion Channels in Vascular Endothelial Cells: An Unexpected Signaling Pathway in Non-Excitable Cells.Biomedicines · 2026Review
- α-Actinin-1 in Megakaryocytes: Its Structure, Interacting Proteins and Implications for Thrombopoiesis.Biomedicines · 2025Review
- Contribution of the TRPM4 Channel to Osteogenic Differentiation of Human Aortic Valve Interstitial Cells.Journal of the American Heart Association · 2025Article
- Association between blood pressure traits, hypertension, antihypertensive drugs and calcific aortic valve stenosis: a mendelian randomization study.Journal of geriatric cardiology : JGC · 2025Article
- Identifying Key Drivers in the Pathogenesis of Martorell Hypertensive Ischaemic Leg Ulcer: A Comparative Analysis with Chronic Venous Leg Ulcer.Acta dermato-venereologica · 2024Article
- The Complex Relationship between Hypoxia Signaling, Mitochondrial Dysfunction and Inflammation in Calcific Aortic Valve Disease: Insights from the Molecular Mechanisms to Therapeutic Approaches.International journal of molecular sciences · 2023Review
- Ion Channels in the Development and Remodeling of the Aortic Valve.International journal of molecular sciences · 2023Review
- Bioinformatics-Based Identification of CircRNA-MicroRNA-mRNA Network for Calcific Aortic Valve Disease.Genetics research · 2023Article
- Implication of Lipids in Calcified Aortic Valve Pathogenesis: Why Did Statins Fail?Journal of clinical medicine · 2022Review
- Global burden of calcific aortic valve disease and attributable risk factors from 1990 to 2019.Frontiers in cardiovascular medicine · 2022Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Calcific aortic valve disease (CAVD) is heritable, as revealed by recent GWAS. While polymorphisms linked to increased expression of CACNA1C - encoding the CaV1.2 L-type voltage-gated Ca2+ channel - and increased Ca2+ signaling are associated with CAVD, whether increased Ca2+ influx through the druggable CaV1.2 causes CAVD is unknown. We confirmed the association between increased CaV1.2 expression and CAVD in surgically removed aortic valves from patients. We extended our studies with a transgenic mouse model that mimics increased CaV1.2 expression within aortic valve interstitial cells (VICs). In young mice maintained on normal chow, we observed dystrophic valve lesions that mimic changes found in presymptomatic CAVD and showed activation of chondrogenic and osteogenic transcriptional regulators within these valve lesions. Chronic administration of verapamil, a CaV1.2 antagonist used clinically, slowed the progression of lesion development in vivo. Exploiting VIC cultures, we demonstrated that increased Ca2+ influx through CaV1.2 drives signaling programs that lead to myofibroblast activation of VICs and upregulation of genes associated with aortic valve calcification. Our data support a causal role for Ca2+ influx through CaV1.2 in CAVD and suggest that early treatment with Ca2+ channel blockers is an effective therapeutic strategy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.