Related Experiment Video
Updated: Dec 6, 2025
Investigating Aortic Valve Calcification via Isolation and Culture of T Lymphocytes using Feeder Cells from Irradiated Buffy Coat
Published on: February 4, 2021
Identification of a peripheral blood gene signature predicting aortic valve calcification
Donal MacGrogan1,2, Beatriz Martínez-Poveda1,2, Jean-Pierre Desvignes3
1Intercellular Signaling in Cardiovascular Development and Disease Laboratory, Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, Spain.
Insights
Calcific aortic valve disease (CAVD) may stem from reiterated developmental processes. A peripheral blood gene signature shows promise for early detection of aortic valve calcification in healthy individuals.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Developmental Biology
Background:
- Calcific aortic valve disease (CAVD) is a major global health concern, necessitating early diagnostic markers for improved patient outcomes.
- Understanding the molecular underpinnings of CAVD is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To investigate the molecular basis of CAVD by comparing gene expression profiles of fetal and adult aortic valves.
- To identify early predictive biomarkers for CAVD and aortic valve calcification in peripheral blood.
Main Methods:
- RNA-sequencing of human fetal aortic valves (gestational weeks 9, 13, 22) and adult noncalcified/calcified aortic valves (bicuspid and tricuspid).
- Comparative analysis of gene expression patterns, including dimension reduction, clustering, and coregulated gene analysis.
- Validation using a case-control study of whole blood transcriptomes from individuals with early aortic valve calcification.
Main Results:
- Diseased adult valves clustered with early fetal valves (week 9), suggesting a role for reiterated developmental processes in CAVD.
- Predominant immune-metabolic signatures (innate/adaptive immunity, T-cell metabolism) were identified in CAVD, with increased cytokine signaling, cell migration/proliferation, and decreased oxidative phosphorylation/protein translation.
- Aberrant expression of cellular stress and neurodegeneration gene signatures in CAVD suggests a link between chronic inflammation and biological aging.
- A peripheral blood gene signature accurately predicted CAVD and moderate aortic valve calcification in asymptomatic individuals.
Conclusions:
- CAVD pathogenesis may involve the reactivation of developmental pathways, coupled with immune-metabolic dysregulation and accelerated biological aging.
- A novel peripheral blood gene signature offers a non-invasive method for early detection of aortic valve calcification, enabling timely intervention.
Abstract:
Calcific aortic valve disease (CAVD) is a significant cause of illness and death worldwide. Identification of early predictive markers could help optimize patient management. RNA-sequencing was carried out on human fetal aortic valves at gestational weeks 9, 13, and 22 and on a case-control study with adult noncalcified and calcified bicuspid and tricuspid aortic valves. In dimension reduction and clustering analyses, diseased valves tended to cluster with fetal valves at week 9 rather than normal adult valves, suggesting that part of the disease program might be due to reiterated developmental processes. The analysis of groups of coregulated genes revealed predominant immune-metabolic signatures, including innate and adaptive immune responses involving lymphocyte T-cell metabolic adaptation. Cytokine and chemokine signaling, cell migration, and proliferation were all increased in CAVD, whereas oxidative phosphorylation and protein translation were decreased. Discrete immune-metabolic gene signatures were present at fetal stages and increased in adult controls, suggesting that these processes intensify throughout life and heighten in disease. Cellular stress response and neurodegeneration gene signatures were aberrantly expressed in CAVD, pointing to a mechanistic link between chronic inflammation and biological aging. Comparison of the valve RNA-sequencing data set with a case-control study of whole blood transcriptomes from asymptomatic individuals with early aortic valve calcification identified a highly predictive gene signature of CAVD and of moderate aortic valve calcification in overtly healthy individuals. These data deepen and broaden our understanding of the molecular basis of CAVD and identify a peripheral blood gene signature for the early detection of aortic valve calcification.
Related Concept Videos
01:22Aortic Regurgitation II: Clinical Features and Diagnostic Tests
01:25Imaging Studies for Cardiovascular System VI: Calcium -Scoring CT
01:21Peripheral Arterial Disease II: Clinical Manifestations and Diagnostic Evaluation
01:20Blood Studies for Cardiovascular System I: Cardiac Biomarkers
The essential diagnostic tools for detecting myocardial necrosis and monitoring individuals suspected of having acute coronary syndrome (ACS) include:
Troponins
Troponins, particularly cardiac troponins I and T, are the most precise and sensitive markers of myocardial injury. They are detectable within 4-6 hours of myocardial injury and remain...
01:15Aortic Regurgitation I: Introduction