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Updated: Aug 19, 2025
Investigating Aortic Valve Calcification via Isolation and Culture of T Lymphocytes using Feeder Cells from Irradiated Buffy Coat
Published on: February 4, 2021
Transcriptomic profiling of calcified aortic valves in clonal hematopoiesis of indeterminate potential carriers
Francesco Vieceli Dalla Sega1, Domenico Palumbo2,3, Francesca Fortini1
1Maria Cecilia Hospital, GVM Care and Research, 48033, Cotignola, Italy.
Insights
Clonal hematopoiesis of indeterminate potential (CHIP) is common in calcific aortic valve disease (CAVD) patients and linked to worse survival after valve replacement. CHIP may drive CAVD through inflammation, potentially involving B cells.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Immunology
Background:
- Clonal hematopoiesis of indeterminate potential (CHIP) is linked to cardiovascular disease and mortality.
- CHIP is prevalent in calcific aortic valve disease (CAVD) and predicts poor outcomes post-valve replacement.
Purpose of the Study:
- To determine CHIP frequency in CAVD patients undergoing valve replacement.
- To investigate CHIP's impact on 12-month survival after valve replacement.
- To explore the pathological mechanisms of CAVD in CHIP carriers via transcriptomics.
Main Methods:
- DNA sequencing to identify CHIP in 168 CAVD patients.
- RNA sequencing (RNA-Seq) to compare aortic valve transcriptomes.
- Immunohistochemistry to validate transcriptomic findings.
Main Results:
- CHIP was confirmed as common in CAVD patients.
- CHIP presence correlated with increased mortality after valve replacement.
- CHIP carriers exhibited a significant immune response in aortic valves, with B cells implicated.
Conclusions:
- CHIP is a significant factor in CAVD, associated with higher mortality post-valve intervention.
- An exaggerated inflammatory response, potentially mediated by B cells, may contribute to CAVD development and progression in CHIP patients.
Abstract:
Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by the presence of clones of mutated blood cells without overt blood diseases. In the last few years, it has emerged that CHIP is associated with atherosclerosis and coronary calcification and that it is an independent determinant of cardiovascular mortality. Recently, CHIP has been found to occur frequently in patients with calcific aortic valve disease (CAVD) and it is associated with a poor prognosis after valve replacement. We assessed the frequency of CHIP by DNA sequencing in the blood cells of 168 CAVD patients undergoing surgical aortic valve replacement or transcatheter aortic valve implantation and investigated the effect of CHIP on 12 months survival. To investigate the pathological process of CAVD in CHIP carriers, we compared by RNA-Seq the aortic valve transcriptome of patients with or without CHIP and non-calcific controls. Transcriptomics data were validated by immunohistochemistry on formalin-embedded aortic valve samples. We confirm that CHIP is common in CAVD patients and that its presence is associated with higher mortality following valve replacement. Additionally, we show, for the first time, that CHIP is often accompanied by a broad cellular and humoral immune response in the explanted aortic valve. Our results suggest that an excessive inflammatory response in CHIP patients may be related to the onset and/or progression of CAVD and point to B cells as possible new effectors of CHIP-induced inflammation.
