Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Aug 26;5(9):888-897.
doi: 10.1016/j.jacbts.2020.06.012. eCollection 2020 Sep.

Interaction of Autotaxin With Lipoprotein(a) in Patients With Calcific Aortic Valve Stenosis

Raphaëlle Bourgeois  1   2 , Romain Devillers  1   3 , Nicolas Perrot  1   2 , Audrey-Anne Després  1   2 , Marie-Chloé Boulanger  1 , Patricia L Mitchell  1 , Jakie Guertin  1   2 , Patrick Couture  1   4 , Michael B Boffa  5 , Corey A Scipione  5 , Philippe Pibarot  1   2 , Marlys L Koschinsky  5 , Patrick Mathieu  1   3 , Benoit J Arsenault  1   2
Affiliations

Interaction of Autotaxin With Lipoprotein(a) in Patients With Calcific Aortic Valve Stenosis

Raphaëlle Bourgeois et al. JACC Basic Transl Sci. .

Abstract

Our objectives were to determine whether autotaxin (ATX) is transported by lipoprotein(a) [Lp(a)] in human plasma and if could be used as a biomarker of calcific aortic valve stenosis (CAVS). We first found that ATX activity was higher in Lp(a) compared to low-density lipoprotein fractions in isolated fractions of 10 healthy participants. We developed a specific assay to measure ATX-Lp(a) in 88 patients with CAVS and 144 controls without CAVS. In a multivariable model corrected for CAVS risk factors, ATX-Lp(a) was associated with CAVS (p = 0.003). We concluded that ATX is preferentially transported by Lp(a) and might represent a novel biomarker for CAVS.

Keywords: ALR, adiponectin-to-leptin ratio; ATX, autotaxin; ATX-apo(a), ATX carried by Lp(a); ATX-apoB, ATX carried by apoB-containing lipoproteins; BMI, body mass index; CAD, coronary artery disease; CAVS, calcific aortic valve stenosis; HDL, high-density lipoprotein; LDL, low-density lipoprotein; Lp(a), lipoprotein(a); LysoPA, lysophosphatidic acid; LysoPC, lysophosphatidylcholine; OxPLs, oxidized phospholipids; apo(a), apolipoprotein(a); apoB, apolipoprotein B; autotaxin; calcific aortic valve stenosis; lipoprotein(a); low-density lipoproteins; obesity.

PubMed Disclaimer

Figures

None
Graphical abstract
Figure 1
Figure 1
Autotaxin Activity and Lysophosphatidic Acid Content in Lipoprotein(a) Versus Low-Density Lipoproteins Purity confirmation by Sebia Hydragel (A), measurement of autotaxin (ATX) activity (B), and lysophoshphatidic acid (LysoPA) content (C) in lipoprotein (a) [Lp(a)] and low-density lipoprotein (LDL) of healthy participants. ATX activity (relative light absorbent unit) and LysoPA content (μM) were normalized by cholesterol content (μmol/l). Asterisk (∗) indicates values significantly different from LDL (p = 0.016 for ATX activity [B] and p = 0.031 for LysoPA content [C]). VLDL = very low density lipoprotein.
Figure 2
Figure 2
Binding Curve of Apo(a) to ATX The binding curve is fitted by a nonlinear model in Prism. Apo(a) = apolipoprotein(a); ATX = autotaxin.
Figure 3
Figure 3
Distribution of ATX-Apo(a) and ATX-ApoB of Study Participants Distribution of ATX-apo(a) (A) and ATX-apoB (B) in patients with (cases) and without (controls) calcific aortic valve stenosis. apoB = apolipoprotein B; other abbreviations as in Figures 1 and 2.
Figure 4
Figure 4
Spearman Correlation Between Plasma Levels of Biomarkers Spearman correlation between plasma levels of ATX-apo(a) and ATX-apoB (A), ATX-apo(a) and Lp(a) (B), ATX-apo(a) and ATX (C) Abbreviations as in Figures 1, 2, and 3.
Figure 5
Figure 5
OR for Aortic Stenosis According to BMI and ATX-Apo(a) Odds ratio (OR) for aortic stenosis (calcific aortic valve stenosis [CAVS]) in patients according to ATX-apo(a) and body mass index (BMI). OR calculated after corrections (same as Model 2). Apo(a) = apolipoprotein(a).
See this image and copyright information in PMC

Comment in

References

    1. Shen M., Tastet L., Bergler-Klein J., Pibarot P., Clavel M.A. Blood, tissue and imaging biomarkers in calcific aortic valve stenosis: past, present and future. Curr Opin Cardiol. 2018;33:125–133. - PubMed
    1. Mathieu P., Boulanger M.C. Basic mechanisms of calcific aortic valve disease. Can J Cardiol. 2014;30:982–993. - PubMed
    1. Lindman B.R., Clavel M.A., Mathieu P. Calcific aortic stenosis. Nat Rev Dis Primers. 2016;2:16006. - PMC - PubMed
    1. Capoulade R., Chan K.L., Yeang C. Oxidized phospholipids, lipoprotein(a), and progression of calcific aortic valve stenosis. J Am Coll Cardiol. 2015;66:1236–1246. - PubMed
    1. Arsenault B.J., Boekholdt S.J., Dube M.P. Lipoprotein(a) levels, genotype, and incident aortic valve stenosis: a prospective Mendelian randomization study and replication in a case-control cohort. Circ Cardiovasc Genet. 2014;7:304–310. - PubMed

LinkOut - more resources