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瓣膜细胞外基质的蛋白质组学结构：FNDC1和MXRA5是主动脉瓣狭窄的新型生物标志物。

Proteomic Architecture of Valvular Extracellular Matrix: FNDC1 and MXRA5 Are New Biomarkers of Aortic Stenosis.

作者信息

Bouchareb Rihab, Guauque-Olarte Sandra, Snider Justin, Zaminski Devyn, Anyanwu Anelechi, Stelzer Paul, Lebeche Djamel

机构信息

Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

GIOD Group, Faculty of Dentistry, Universidad Cooperativa de Colombia, Pasto, Colombia.

出版信息

JACC Basic Transl Sci. 2021 Jan 13;6(1):25-39. doi: 10.1016/j.jacbts.2020.11.008. eCollection 2021 Jan.

DOI:10.1016/j.jacbts.2020.11.008
PMID:33532664
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7838057/
Abstract

This study analyzed the expression of extracellular matrix (ECM) proteins during aortic valve calcification with mass spectrometry, and further validated in an independent human cohort using RNAseq data. The study reveals that valve calcification is associated with significant disruption in ECM and metabolic pathways, and highlights a strong connection between metabolic markers and ECM remodeling. It also identifies FNDC1 and MXRA5 as novel ECM biomarkers in calcified valves, electing them as potential targets in the development and progression of aortic stenosis.

摘要

本研究采用质谱分析法分析了主动脉瓣钙化过程中细胞外基质（ECM）蛋白的表达情况，并利用RNA测序数据在一个独立的人类队列中进行了进一步验证。该研究表明，瓣膜钙化与ECM和代谢途径的显著破坏有关，并突出了代谢标志物与ECM重塑之间的紧密联系。研究还将FNDC1和MXRA5鉴定为钙化瓣膜中新的ECM生物标志物，使其成为主动脉瓣狭窄发生和发展的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/462b/7838057/20571508103a/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/462b/7838057/954b664b3ba0/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/462b/7838057/9c32035229de/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/462b/7838057/049c4a6857fc/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/462b/7838057/9e5212c800e7/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/462b/7838057/ba3c97f436c3/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/462b/7838057/9e1997468d60/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/462b/7838057/1efe01f23948/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/462b/7838057/425185e41dd2/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/462b/7838057/20571508103a/gr8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/462b/7838057/954b664b3ba0/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/462b/7838057/9c32035229de/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/462b/7838057/049c4a6857fc/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/462b/7838057/9e5212c800e7/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/462b/7838057/ba3c97f436c3/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/462b/7838057/9e1997468d60/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/462b/7838057/1efe01f23948/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/462b/7838057/425185e41dd2/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/462b/7838057/20571508103a/gr8.jpg

相似文献

[1]
Proteomic Architecture of Valvular Extracellular Matrix: FNDC1 and MXRA5 Are New Biomarkers of Aortic Stenosis.

JACC Basic Transl Sci. 2021-1-13

[2]
RNA expression profile of calcified bicuspid, tricuspid, and normal human aortic valves by RNA sequencing.

Physiol Genomics. 2016-10-1

[3]
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J Surg Res. 2017-6-1

[4]
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[5]
iTRAQ proteomic analysis of extracellular matrix remodeling in aortic valve disease.

Sci Rep. 2015-12-1

[6]
Different Notch signaling in cells from calcified bicuspid and tricuspid aortic valves.

J Mol Cell Cardiol. 2017-11-20

[7]
Release of leukotriene B4, transforming growth factor-beta1 and microparticles in relation to aortic valve calcification.

J Heart Valve Dis. 2013-11

[8]
Progression of aortic valve stenosis: TGF-beta1 is present in calcified aortic valve cusps and promotes aortic valve interstitial cell calcification via apoptosis.

Ann Thorac Surg. 2003-2

[9]
Lipid mass spectrometry imaging and proteomic analysis of severe aortic stenosis.

J Mol Histol. 2020-10

[10]
Spatiotemporal Multi-Omics Mapping Generates a Molecular Atlas of the Aortic Valve and Reveals Networks Driving Disease.

Circulation. 2018-7-24

引用本文的文献

[1]
Recent Advances in Deciphering Normal and Diseased Aortic Valve Biology Using Transcriptomic Technologies.

J Cell Mol Med. 2025-9

[2]
A Transcriptomic Approach to Sex Differences in Calcific Aortic Valve Stenosis in Patients with a Tricuspid Aortic Valve.

CJC Open. 2025-2-17

[3]
Extracellular Matrix Dynamics in Aortic Valve Health and Disease: Insights into Fibrocalcific Remodeling and Creation of Biomimetic Platforms.

J Heart Valve Soc. 2024

[4]
The prognostic and immune significance of fibronectin type III domain-containing 1 gene in pan-cancer and its relationship with proliferation and migration of stomach adenocarcinoma.

Transl Cancer Res. 2025-5-30

[5]
Opportunities and challenges for the use of human samples in translational cardiovascular research: a scientific statement of the ESC Working Group on Cellular Biology of the Heart, the ESC Working Group on Cardiovascular Surgery, the ESC Council on Basic Cardiovascular Science, the ESC Scientists of Tomorrow, the European Association of Percutaneous Cardiovascular Interventions of the ESC, and the Heart Failure Association of the ESC.

Cardiovasc Res. 2025-5-23

[6]
Identification and validation of the diagnostic biomarker MFAP5 for CAVD with type 2 diabetes by bioinformatics analysis.

Front Immunol. 2024-12-19

[7]
Extracellular matrix in vascular homeostasis and disease.

Nat Rev Cardiol. 2025-5

[8]
Sex-Related Differences in the Pathophysiology, Cardiac Imaging, and Clinical Outcomes of Aortic Stenosis: A Narrative Review.

J Clin Med. 2024-10-24

[9]
Identification of HTRA1, DPT and MXRA5 as potential biomarkers associated with osteoarthritis progression and immune infiltration.

BMC Musculoskelet Disord. 2024-8-15

[10]
Integrated Bioinformatics Analysis Reveals the Aberrantly Methylated Differentially Expressed Genes in Dilated Cardiomyopathy.

Int J Med Sci. 2024

本文引用的文献

[1]
Rutin suppresses FNDC1 expression in bone marrow mesenchymal stem cells to inhibit postmenopausal osteoporosis.

Am J Transl Res. 2019-10-15

[2]
Extracellular Matrix Remodeling of Adipose Tissue in Obesity and Metabolic Diseases.

Int J Mol Sci. 2019-10-2

[3]
Extracellular matrix mechanical cues regulate lipid metabolism through Lipin-1 and SREBP.

Nat Cell Biol. 2019-2-4

[4]
SERPINB1-mediated checkpoint of inflammatory caspase activation.

Nat Immunol. 2019-1-28

[5]
Activated platelets promote an osteogenic programme and the progression of calcific aortic valve stenosis.

Eur Heart J. 2019-5-1

[6]
Extracellular Matrix Remodeling in Human Disease.

J Microsc Ultrastruct. 2018

[7]
The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality.

Cell Metab. 2018-9-4

[8]
Endothelial Cell Metabolism in Atherosclerosis.

Front Cell Dev Biol. 2018-8-7

[9]
DNA methylation of a PLPP3 MIR transposon-based enhancer promotes an osteogenic programme in calcific aortic valve disease.

Cardiovasc Res. 2018-9-1

[10]
Influence of metabolic syndrome and diabetes on progression of calcific aortic valve stenosis.

Int J Cardiol. 2017-6-30

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