ArticleJournal of molecular and cellular cardiology2021
Spatial N-glycomics of the human aortic valve in development and pediatric endstage congenital aortic valve stenosis.
Article in Journal of molecular and cellular cardiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Consensus statement on mass spectrometry-based proteomic analysis of cardiac tissue.Nature cardiovascular research · 2026Article
- Multimodal landscape of atherosclerotic plaques: A spatial omics approach with mass spectrometry imaging.Analytica chimica acta · 2025Review
- A neonatal rat model of progressive left ventricular pressure overload induced by abdominal aortic banding microsurgery.JTCVS techniques · 2025Article
- Serum N-glycomic profiling identifies candidate biomarker panels for assessing coronary artery stenosis severity.Heliyon · 2024Article
- Review
- Tolerable glycometabolic stress boosts cancer cell resilience through altered N-glycosylation and Notch signaling activation.Cell death & disease · 2024Article
- Focusing on the Native Matrix Proteins in Calcific Aortic Valve Stenosis.JACC. Basic to translational science · 2023Review
- Network-Guided Multiomic Mapping of Aortic Valve Calcification.Arteriosclerosis, thrombosis, and vascular biology · 2023Review
- Congenital aortic valve stenosis: from pathophysiology to molecular genetics and the need for novel therapeutics.Frontiers in cardiovascular medicine · 2023Review
- Metabolic Links to Socioeconomic Stresses Uniquely Affecting Ancestry in Normal Breast Tissue at Risk for Breast Cancer.Frontiers in oncology · 2022Article
- Perspectives on pediatric congenital aortic valve stenosis: Extracellular matrix proteins, post translational modifications, and proteomic strategies.Frontiers in cardiovascular medicine · 2022Review
- Mass Spectrometry Imaging of Fibroblasts: Promise and Challenge.Expert review of proteomics · 2021Review
- Glycan Imaging Mass Spectrometry: Progress in Developing Clinical Diagnostic Assays for Tissues, Biofluids, and Cells.Clinics in laboratory medicine · 2021Review
- Multi-Omics Approaches to Define Calcific Aortic Valve Disease Pathogenesis.Circulation research · 2021Review
- The Crossroads of Glycoscience, Infection, and Immunology.Frontiers in microbiology · 2021Article
- Analysis of carbohydrates and glycoconjugates by matrix-assisted laser desorption/ionization mass spectrometry: An update for 2021-2022.Mass spectrometry reviewsReview
- Mass spectrometry imaging of N-linked glycans: Fundamentals and recent advances.Mass spectrometry reviewsReview
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Congenital aortic valve stenosis (AS) progresses as an obstructive narrowing of the aortic orifice due to deregulated extracellular matrix (ECM) production by aortic valve (AV) leaflets and leads to heart failure with no effective therapies. Changes in glycoprotein and proteoglycan distribution are a hallmark of AS, yet valvular carbohydrate content remains virtually uncharacterized at the molecular level. While almost all glycoproteins clinically linked to stenotic valvular modeling contain multiple sites for N-glycosylation, there are very few reports aimed at understanding how N-glycosylation contributes to the valve structure in disease. Here, we tested for spatial localization of N-glycan structures within pediatric congenital aortic valve stenosis. The study was done on valvular tissues 0-17 years of age with de-identified clinical data reporting pre-operative valve function spanning normal development, aortic valve insufficiency (AVI), and pediatric endstage AS. High mass accuracy imaging mass spectrometry (IMS) was used to localize N-glycan profiles in the AV structure. RNA-Seq was used to identify regulation of N-glycan related enzymes. The N-glycome was found to be spatially localized in the normal aortic valve, aligning with fibrosa, spongiosa or ventricularis. In AVI diagnosed tissue, N-glycans localized to hypertrophic commissures with increases in pauci-mannose structures. In all valve types, sialic acid (N-acetylneuraminic acid) N-glycans were the most abundant N-glycan group. Three sialylated N-glycans showed common elevation in AS independent of age. On-tissue chemical methods optimized for valvular tissue determined that aortic valve tissue sialylation shows both α2,6 and α2,3 linkages. Specialized enzymatic strategies demonstrated that core fucosylation is the primary fucose configuration and localizes to the normal fibrosa with disparate patterning in AS. This study identifies that the human aortic valve structure is spatially defined by N-glycomic signaling and may generate new research directions for the treatment of human aortic valve disease.
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Registered trials
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