Metabolomic Signature of Human Aortic Valve Stenosis

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

doi:10.1016/j.jacbts.2020.10.001

Metabolomic Signature of Human Aortic Valve Stenosis

JACC Basic Transl Sci. 2020 Dec 16;5(12):1163-1177. doi: 10.1016/j.jacbts.2020.10.001. eCollection 2020 Dec.

Authors

Arun Surendran^{1

2

3}, Andrea Edel^{1

2}, Mahesh Chandran³, Pascal Bogaert¹, Pedram Hassan-Tash², Aneesh Kumar Asokan³, Brett Hiebert¹, Zahra Solati^{1

2}, Shubhkarman Sandhawalia¹, Michael Raabe⁴, Malek Kass⁵, Ashish Shah^{2

5}, Davinder S Jassal^{2

5}, Abdul Jaleel³, Amir Ravandi^{1

2

5}

Affiliations

¹ Cardiovascular Lipidomics Laboratory, St. Boniface Hospital, Albrechtsen Research Centre, Winnipeg, Manitoba, Canada.
² Department of Physiology and Pathophysiology, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
³ Mass Spectrometry and Proteomics Core Facility, Rajiv Gandhi Centre for Biotechnology, Kerala, India.
⁴ Section of Cardiac Surgery, Rady Faculty of Health Sciences, University of Manitoba, Manitoba, Winnipeg, Canada.
⁵ Section of Cardiology, Department of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.

Abstract

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 hemodynamic progression and could select patients at risk for faster progression rate.

Keywords: AS, aortic stenosis; ATX, autotaxin; AV, aortic valve; AVA, aortic valve area; BAV, bicuspid aortic valve; CAVS, calcific aortic valve stenosis; CV, correlation of variation; Lp(a), lipoprotein(a); LysoPA, lysophosphatidic acid; LysoPC, lysophosphatidylcholine; LysoPE, lysophosphatidylethanolamine; MG, monoglyceride; MPG, mean pressure gradient; PC, phosphatidylcholine; QC, quality control; TAV, tricuspid aortic valve; Vmax, peak aortic jet velocity; aortic stenosis; calcific aortic valve stenosis; lysophosphatidic acids; nontargeted metabolomics; targeted lipidomics; valvular calcification.