ArticleEuropean heart journal2025
Mosaic loss of Y chromosome and mortality after coronary angiography.
Article in European heart journal, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Beyond sex determination: the Y chromosome in male cancers.Nature reviews. Cancer · 2026Review
- Human genetics across levels of biological organization.Nature reviews. Genetics · 2026Review
- Mosaic Loss of Chromosome Y, Smoking, and Risk of Symptomatic Peripheral Artery Disease: Insights From a Longitudinal Cohort Study.Journal of the American Heart Association · 2026Article
- Age-related loss of Y chromosome is associated with mortality after ST-segment elevation myocardial infarction.Communications medicine · 2026Article
- Loss of chromosome Y in hematopoietic cells: mechanisms and implications for human disease.MedScience · 2026Review
- Relevance of Clonal Hematopoiesis in Immune Cells for Degenerative Aortic Valve Stenosis.Journal of the American Heart Association · 2026Review
- Loss of Y Chromosome and Major Cardiovascular Events in a Prospective Study of Older Men.Journal of the American College of Cardiology · 2026Article
- The Immunological Consequences of Clonal Hematopoiesis in Heart Failure.Immunological reviews · 2026Review
- Cellular Senescence, Inflammaging and Cardiovascular Disease.Immunological reviews · 2026Review
- Genomic Instability and Clonal Hematopoiesis in the Deep-Space Environment: The Role of Sex-Chromosome Asymmetry and High-LET Radiation.Current stem cell reports · 2026Article
- Loss of Y chromosome: proteomic signatures in human cardiovascular disease.European heart journal · 2025Article
- Clonal Hematopoiesis in Cancer and Cardiovascular Disease: JACC: CardioOncology State-of-the-Art Review.JACC. CardioOncology · 2025Review
- Contributions of Noncardiac Organ-Heart Immune Crosstalk and Somatic Mosaicism to Heart Failure: Current Knowledge and Perspectives.Circulation research · 2025Review
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
BACKGROUND AND
aimsAcquired somatic mutations emerged as important drivers of adverse cardiovascular disease outcomes. Recently, mosaic loss of Y chromosome (LOY) in haematopoietic cells was identified to induce diffuse cardiac fibrosis in male mice. The aim of the present study was to determine the association between LOY and cardiovascular mortality in patients undergoing coronary angiography.
methodsLOY was quantified in 1698 male participants of the LURIC study, who underwent coronary angiography, and its association with all-cause and cardiovascular mortality was determined. Furthermore, the interaction between LOY and inherited genetic susceptibility for cardiac fibrosis was assessed.
resultsThe frequency of LOY steeply increased in male participants of LURIC at the age of 60 years. Loss of Y chromosome > 17% was associated with significantly higher all-cause [hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.09-1.82] and cardiovascular mortality (HR 1.49, 95% CI 1.09-2.03), which was driven by a higher risk for fatal myocardial infarction (HR 2.65, 95% CI 1.46-4.81). Loss of Y chromosome > 17% was associated with a profibrotic and proinflammatory plasma protein expression profile as characterized by higher plasma levels of osteoprotegerin, matrix metalloproteinase-12, growth differentiation factor 15, heparin-binding EGF-like growth factor, and resistin. Genetic predisposition for lower myocardial fibrosis attenuated the association between LOY and cardiovascular mortality. Genome-wide methylation analyses identified differential methylation in 298 genes including ACTB, RPS5, WDR1, CD151, and ARAP1. Single-cell RNA sequencing further confirmed differential gene expression of 37 of these genes in LOY in peripheral blood mononuclear cells comprising a set of fibrosis-regulating genes including RPS5. RPS5 silencing in macrophages induced a paracrine induction of collagen expression in cardiac fibroblasts documenting a functional role in vitro.
conclusionsLOY represents an important independent risk factor for cardiovascular mortality in male patients with coronary artery disease. Targeting LOY may represent a sex-specific personalized medicine approach.
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