Network-guided multiomic mapping of aortic valve calcification
Open accessAbstract
Despite devastating clinical sequelae of calcific aortic valve disease that range from left ventricular remodeling to arrhythmias, heart failure, and early death, the molecular insights into disease initiation and progression are limited and pharmacotherapies remain unavailable. The pathobiology of calcific aortic valve disease is complex and comprehensive studies are challenging valvular calcification is heterogeneous and occurs preferentially on the aortic surface, along a fibrocalcific spectrum. Here, we review efforts to study (epi-)genomic, transcriptomic, proteomic, and metabolomic aspects of aortic valve calcification in combination with network medicine-/systems biology-based strategies to integrate multilayered omics datasets and prioritize druggable targets for experimental validation studies. Ultimately, such holistic approach efforts may open therapeutic avenues that go beyond invasive and costly valve replacement therapy.
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An effort to identify a gene expression signature for the aortic valve and transfer this knowledge to discover specific biomarkers and therapeutic targets has not been attempted.
“Although studies attempted to elucidate the transcriptomic profile of human aortic valves with aortic stenosis,11,12,13,14,15,16 an effort to identify a gene expression signature for the aortic valve and transfer this knowledge to discover specific biomarkers and therapeutic targets has not been attempted.”
From Aortic valve-specific genes dysregulated in calcific aortic valve stenosis as potential biomarkers and therapeutic targets (2025) · cites this paper as [16]
The section “Mapping the Valvular Transcriptome” (page not available) reports disease-stage-specific transcriptional signatures in aortic valve tissue. “Towards a Holistic Understanding of CAVD” (page not available) also describes RNA-seq and gene-network screening that identified a potential therapeutic candidate. These reported attempts contradict the claim that identifying a valve expression signature and applying such knowledge to target discovery had not been attempted, although the passages do not establish a biomarker from that work. (LLM, conf=0.84)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredNetwork-based integrative methods are increasingly used to enhance understanding of CAVD onset, progression, and treatment.
“Network-based integrative methods are increasingly used to enhance understanding of CAVD onset, progression, and treatment [44].”
From Identifying novel drug targets for calcific aortic valve disease through Mendelian randomization (2025) · cites this paper as [44]
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- Authors
- Blaser, M. C., Kraler, S., Lüscher, T. F., & Aikawa, E.
- Affiliations
- Brigham and Women's Hospital (US)
- University of Zurich (CH)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2023-03
- Volume
- 43
- Issue
- 3
- Pages
- 417-426
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- PMC
- PMC9975082
- OpenAlex
- W4318913403
- Cited by
- 16
- References
- 49
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 6
- FWCI
- 0.84
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by-nc-nd)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- Foundation for Cardiovascular Research
- Schweizerische Herzstiftung (FF20094)
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL136431, R01HL147095, R01HL141917)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Valve Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- aortic valve calcification, calcific aortic valve disease, multi-omics integration, network medicine, systems biology, druggable targets, transcriptomics, proteomics, metabolomics, epigenomics
- MeSH terms
- Multiomics, Aortic Valve, Aortic Valve Stenosis, Calcinosis, Humans, Proteomics
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