Dataset Information

Metabolomics Characterization of Human Calcific Aortic Valve Stenosis

ABSTRACT:

BACKGROUND: Calcific aortic valve stenosis (CAVS) is the most prevalent valvular heart disease in developed countries with significant morbidity and mortality. Given the poor understanding of the pathophysiological processes leading to CAVS, we utilized a joint non-targeted metabolomics and targeted lipidomics approach to better characterize the metabolic perturbations involved in its development and progression.

METHODS: We collected human aortic valve tissue from 106 patients undergoing aortic valve replacement surgery. Our cohort represented aortic valvular hemodynamics from mild to severe aortic stenosis with varying degrees of valvular calcification.

RESULTS: Seventy-two significantly differential (p<0.01) metabolites across different stages of CAVS severity were filtered and identified from the tissue metabolome. Each stage of valvular stenosis was characterized by a distinct metabolic signature. The top three perturbed metabolic pathways in the setting of CAVS involved glycerophospholipid metabolism, linoleic acid metabolism and primary bile acid biosynthesis. The lysophosphatidic acid species (LysoPA) exhibited significant (p<0.05) association with CAVS severity and were also found to select patients with accelerated rate of CAVS progression. Two LysoPA species namely, 18:2 LysoPA and 20:4 LysoPA, exhibited potential to serve as biomarkers of CAVS severity.

CONCLUSIONS: The present study reports the largest and most comprehensive metabolomics analysis of human aortic valve stenosis that highlights the dysregulated LysoPA pathway involved in the pathogenesis of CAVS.

INSTRUMENT(S): HILIC_Neg_Synapt_HDMS, RP_Neg_Synapt_HDMS, RP_Pos_Synapt_HDMS, HILIC_Pos_Synapt_HDMS

SUBMITTER: Aneesh Kumar

PROVIDER: MTBLS1267 | MetaboLights | 2020-02-03

REPOSITORIES: MetaboLights

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Dataset's files

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			Action	DRS
	MTBLS1267	Other
	FILES	Other
	a_MTBLS1267_NEG_HILIC_mass_spectrometry.txt	Txt
	a_MTBLS1267_NEG_RP_mass_spectrometry.txt	Txt
	a_MTBLS1267_POS_HILIC_mass_spectrometry.txt	Txt

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Publications

Metabolomic Signature of Human Aortic Valve Stenosis.

Surendran Arun A Edel Andrea A Chandran Mahesh M Bogaert Pascal P Hassan-Tash Pedram P Kumar Asokan Aneesh A Hiebert Brett B Solati Zahra Z Sandhawalia Shubhkarman S Raabe Michael M Kass Malek M Shah Ashish A Jassal Davinder S DS Jaleel Abdul A Ravandi Amir A

JACC. Basic to translational science 20201216 12

This study outlines the first step toward creating the metabolite atlas of human calcified aortic valves by identifying the expression of metabolites and metabolic pathways involved at various stages of calcific aortic valve stenosis progression. Untargeted analysis identified 72 metabolites and lipids that were significantly altered (p < 0.01) across different stages of disease progression. Of these metabolites and lipids, the levels of lysophosphatidic acid were shown to correlate with faster ...[more]

PMID: 33426374

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