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Updated: Aug 12, 2025
Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Network-Guided Multiomic Mapping of Aortic Valve Calcification
Mark C Blaser1, Simon Kraler2, Thomas F Lüscher2,3,4
1Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (M.C.B., E.A.).
Insights
Molecular insights into calcific aortic valve disease (CAVD) are limited, hindering new drug development. This review integrates multi-omics data and systems biology to identify potential therapeutic targets for CAVD, aiming to move beyond valve replacement.
Area of Science:
- Cardiovascular Biology
- Genomics and Systems Biology
- Translational Medicine
Background:
- Calcific aortic valve disease (CAVD) causes severe heart conditions, including heart failure and death, yet lacks effective drug therapies.
- The complex and heterogeneous nature of valvular calcification presents significant challenges for research and treatment development.
Purpose of the Study:
- To review current research on the molecular mechanisms underlying CAVD initiation and progression.
- To explore the integration of multi-omics data (genomics, transcriptomics, proteomics, metabolomics) with network medicine and systems biology approaches.
- To identify and prioritize druggable targets for potential pharmacotherapies for CAVD.
Main Methods:
- Comprehensive review of studies investigating (epi-)genomic, transcriptomic, proteomic, and metabolomic profiles in aortic valve calcification.
- Application of network medicine and systems biology strategies to integrate diverse omics datasets.
- Prioritization of potential therapeutic targets based on integrated data analysis for experimental validation.
Main Results:
- Multi-omics data reveal complex molecular pathways involved in the fibrocalcific spectrum of CAVD.
- Systems biology approaches enable the identification of interconnected molecular networks driving disease progression.
- Several prioritized druggable targets warrant further investigation for therapeutic potential.
Conclusions:
- A holistic, multi-omics approach is crucial for understanding CAVD pathobiology.
- Integrating diverse datasets through systems biology can uncover novel therapeutic strategies.
- This research may pave the way for pharmacotherapies to treat CAVD, offering an alternative to valve replacement.
Abstract:
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.
