Pathobiology of Lp(a) in calcific aortic valve disease

ABSTRACT

Introduction: Calcific aortic valve disease (CAVD) is the most prevalent heart valve disorder. Gene variant in the LPA gene, which encodes for apolipoprotein(a), has been associated at the genome-wide level with CAVD. The process whereby Lp(a) promotes the development of CAVD is under intensive investigation and recent data have shed important insights into disease biology. In this regard, autotaxin (ATX), a lysophospholipase D, interacts with Lp(a) and promotes the mineralization of the aortic valve.

Areas covered: In this paper, we are reviewing the biology of Lp(a) and the latest discoveries about the molecular processes that link this lipoprotein with the development of CAVD including the role of ATX.

Expert commentary: Elevated Lp(a) levels are genetically determined and considered as an important risk factor for CAVD. Understanding how Lp(a) promotes the development/progression of CAVD is crucial as it may hold promise for the development of new therapies.

KEYWORDS:

• Calcific aortic valve disease
• calcific aortic stenosis
• Lp(a)
• apolipoprotein(a)
• autotaxin

Declaration of interest

The work of the authors is supported by the Canadian Institutes of Health Research grants to P.M. (FRN114893, FRN142244, FRN148778, FRN130254) and to M.L.K. (FRN126076), the Heart and Stroke Foundation of Canada (G-13-0003091 to M.L.K) and (G-14-0005913 to P.M.) the Quebec Heart and Lung Institute Fund. B.J.A. holds a Junior scholarship from Fonds de Recherche du Québec-Santé (FRQS). Y.B. holds a Canada Research Chair in Genomics of Heart and Lung Diseases. P.M. holds a Fonds de Recherche du Québec-Santé (FRQS) Research Chair on the Pathobiology of Calcific Aortic Valve Disease. P.M. is a consultant for Ionis Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was funded by Heart and Stroke Foundation of Canada (G-13-0003091, G-14-0005913) and Institute of Circulatory and Respiratory Health (FRN114893, FRN142244, FRN148778, FRN130254, FRN1260).