Lipoprotein(a) Induces Human Aortic Valve Interstitial Cell Calcification

Bin Yu, PhD; Anouar Hafiane, PhD; George Thanassoulis, MD; Leah Ott, BS; Nial Filwood, MD; Marta Cerruti, PhD; Ophélie Gourgas, MS; Dominique Shum-Tim, MD; Hamood Al Kindi, MD; Benoit de Varennes, MD; Alawi Alsheikh-Ali, MD, PhD; Jacques Genest, MD; Adel Schwertani, DM, PhD

doi:10.1016/j.jacbts.2017.03.015

JACC: Basic to Translational Science (Aug 2017)

Lipoprotein(a) Induces Human Aortic Valve Interstitial Cell Calcification

Bin Yu, PhD,
Anouar Hafiane, PhD,
George Thanassoulis, MD,
Leah Ott, BS,
Nial Filwood, MD,
Marta Cerruti, PhD,
Ophélie Gourgas, MS,
Dominique Shum-Tim, MD,
Hamood Al Kindi, MD,
Benoit de Varennes, MD,
Alawi Alsheikh-Ali, MD, PhD,
Jacques Genest, MD,
Adel Schwertani, DM, PhD

Affiliations

Bin Yu, PhD: Divisions of Cardiology and Cardiac Surgery, Department of Medicine, Surgery and Pathology, McGill University, Montreal, Quebec, Canada
Anouar Hafiane, PhD: Divisions of Cardiology and Cardiac Surgery, Department of Medicine, Surgery and Pathology, McGill University, Montreal, Quebec, Canada
George Thanassoulis, MD: Divisions of Cardiology and Cardiac Surgery, Department of Medicine, Surgery and Pathology, McGill University, Montreal, Quebec, Canada
Leah Ott, BS: Divisions of Cardiology and Cardiac Surgery, Department of Medicine, Surgery and Pathology, McGill University, Montreal, Quebec, Canada
Nial Filwood, MD: Divisions of Cardiology and Cardiac Surgery, Department of Medicine, Surgery and Pathology, McGill University, Montreal, Quebec, Canada
Marta Cerruti, PhD: Department of Materials Engineering, McGill University, Montreal, Quebec, Canada
Ophélie Gourgas, MS: Department of Materials Engineering, McGill University, Montreal, Quebec, Canada
Dominique Shum-Tim, MD: Divisions of Cardiology and Cardiac Surgery, Department of Medicine, Surgery and Pathology, McGill University, Montreal, Quebec, Canada
Hamood Al Kindi, MD: Divisions of Cardiology and Cardiac Surgery, Department of Medicine, Surgery and Pathology, McGill University, Montreal, Quebec, Canada
Benoit de Varennes, MD: Divisions of Cardiology and Cardiac Surgery, Department of Medicine, Surgery and Pathology, McGill University, Montreal, Quebec, Canada
Alawi Alsheikh-Ali, MD, PhD: College of Medicine, Mohammed Bin Rashid University of Medical and Health Sciences, Dubai, United Arab Emirates
Jacques Genest, MD: Divisions of Cardiology and Cardiac Surgery, Department of Medicine, Surgery and Pathology, McGill University, Montreal, Quebec, Canada
Adel Schwertani, DM, PhD: Divisions of Cardiology and Cardiac Surgery, Department of Medicine, Surgery and Pathology, McGill University, Montreal, Quebec, Canada

DOI: https://doi.org/10.1016/j.jacbts.2017.03.015
Journal volume & issue: Vol. 2, no. 4
pp. 358 – 371

Abstract

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Lipoprotein(a), or Lp(a), significantly increased alkaline phosphatase activity, release of phosphate, calcium deposition, hydroxyapatite, cell apoptosis, matrix vesicle formation, and phosphorylation of signal transduction proteins; increased expression of chondro-osteogenic mediators; and decreased SOX9 and matrix Gla protein (p < 0.001). Inhibition of MAPK38 and GSK3β significantly reduced Lp(a)-induced calcification of human aortic valve interstitial cells (p < 0.001). There was abundant presence of Lp(a) and E06 immunoreactivity in diseased human aortic valves. The present study demonstrates a causal effect for Lp(a) in aortic valve calcification and suggests that interfering with the Lp(a)pathway could provide a novel therapeutic approach in the management of this debilitating disease.

Published in JACC: Basic to Translational Science

ISSN: 2452-302X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the circulatory (Cardiovascular) system
Website: https://www.journals.elsevier.com/jacc-basic-to-translational-science/

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