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

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

doi:10.1016/j.jacbts.2020.11.008

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

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

Authors

Rihab Bouchareb¹, Sandra Guauque-Olarte², Justin Snider³, Devyn Zaminski¹, Anelechi Anyanwu⁴, Paul Stelzer⁴, Djamel Lebeche^{1

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Affiliations

¹ Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
² GIOD Group, Faculty of Dentistry, Universidad Cooperativa de Colombia, Pasto, Colombia.
³ Biological Mass Spectrometry Shared Resource, Stony Brook University Cancer Center, New York, New York, USA.
⁴ Department of Cardiovascular Surgery, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁵ Diabetes, Obesity and Metabolism Institute, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
⁶ Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

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.

Keywords: AS, aortic stenosis; EC, endothelial cell; ECM; ECM, extracellular matrix; FN, fibronectin; FNDC1, fibronectin type III domain containing 1; KEGG, Kyoto Encyclopedia of Genes and Genomes; LDL, low-density lipoprotein; MXRA5, matrix-remodeling-associated protein 5; MetS, metabolic syndrome; PBS, phosphate-buffered saline; RNA-Seq; RNAseq, RNA sequencing; TAVc, calcified tricuspid aortic valve; TAVn, noncalcified tricuspid aortic valve; VAHC, calcified human aortic valve; VAHN, normal human aortic valve; aortic stenosis; calcified aortic valves; hVIC, human valve interstitial cell; metabolism; proteomics.

Grants and funding

T32 HL007824/HL/NHLBI NIH HHS/United States