Lipoprotein(a)-Associated Molecules AreÂ Prominent Components in Plasma andÂ Valve Leaflets in Calcific Aortic ValveÂ Stenosis

Michael Torzewski, MD; Amir Ravandi, MD, PhD; Calvin Yeang, MD, PhD; Andrea Edel, PhD; Rahul Bhindi, MD; Stefan Kath, MD; Laura Twardowski, MD; Jens Schmid, PhD; Xiaohong Yang, BS; Ulrich F.W. Franke, MD; Joseph L. Witztum, MD; Sotirios Tsimikas, MD

JACC: Basic to Translational Science (Jun 2017)

Lipoprotein(a)-Associated Molecules AreÂ Prominent Components in Plasma andÂ Valve Leaflets in Calcific Aortic ValveÂ Stenosis

Michael Torzewski, MD,
Amir Ravandi, MD, PhD,
Calvin Yeang, MD, PhD,
Andrea Edel, PhD,
Rahul Bhindi, MD,
Stefan Kath, MD,
Laura Twardowski, MD,
Jens Schmid, PhD,
Xiaohong Yang, BS,
Ulrich F.W. Franke, MD,
Joseph L. Witztum, MD,
Sotirios Tsimikas, MD

Affiliations

Michael Torzewski, MD: Department of Laboratory Medicine, Robert-Bosch-Hospital, Stuttgart, Germany
Amir Ravandi, MD, PhD: Cardiac Sciences Program, University of Manitoba and Institute of Cardiovascular Sciences, St. Boniface Hospital, Winnipeg, Canada
Calvin Yeang, MD, PhD: Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology and University of Tuebingen, Stuttgart, Germany
Andrea Edel, PhD: Cardiac Sciences Program, University of Manitoba and Institute of Cardiovascular Sciences, St. Boniface Hospital, Winnipeg, Canada
Rahul Bhindi, MD: Cardiac Sciences Program, University of Manitoba and Institute of Cardiovascular Sciences, St. Boniface Hospital, Winnipeg, Canada
Stefan Kath, MD: Department of Laboratory Medicine, Robert-Bosch-Hospital, Stuttgart, Germany
Laura Twardowski, MD: Department of Laboratory Medicine, Robert-Bosch-Hospital, Stuttgart, Germany
Jens Schmid, PhD: Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology and University of Tuebingen, Stuttgart, Germany
Xiaohong Yang, BS: Division of Cardiovascular Medicine, Sulpizio Cardiovascular Center, University of California San Diego, La Jolla, California
Ulrich F.W. Franke, MD: Department of Cardiovascular Surgery, Robert-Bosch-Hospital, Stuttgart, Germany
Joseph L. Witztum, MD: Division of Endocrinology and Metabolism, University of California San Diego, La Jolla, California
Sotirios Tsimikas, MD: Division of Cardiovascular Medicine, Sulpizio Cardiovascular Center, University of California San Diego, La Jolla, California; Address for correspondence: Dr. Sotirios Tsimikas, Vascular Medicine Program, Department of Medicine, Sulpizio Cardiovascular Center, University of California San Diego, 9500 Gilman Drive, BSB 1080, La Jolla, California 92093-0682.

Journal volume & issue: Vol. 2, no. 3
pp. 229 – 240

Abstract

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Summary: The LPA gene is the only monogenetic risk factor for calcific aortic valve stenosis (CAVS). Oxidized phospholipids (OxPL) and lysophosphatidic acid generated by autotaxin (ATX) from OxPL are pro-inflammatory. Aortic valve leaflets categorized pathologically from both ATXâapolipoprotein B and ATXâapolipoprotein(a) were measureable in plasma. Lipoprotein(a) (Lp[a]), ATX, OxPL, and malondialdehyde epitopes progressively increased in immunostaining (pÂ < 0.001 for all). Six species of OxPL and lysophosphatidic acid were identified after extraction from valve leaflets. The presence of a constellation of pathologically linked, Lp(a)-associated molecules in plasma and in aortic valve leaflets of patients with CAVS suggest that Lp(a) is a key etiologic factor in CAVS. Key Words: aortic valve stenosis, autotaxin, inflammation, Lp(a), oxidation-specific epitopes

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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