Lipoprotein(a)-Associated Molecules Are Prominent Components in Plasma and Valve Leaflets in Calcific Aortic Valve Stenosis

oleh: 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

Format: Article
Diterbitkan: Elsevier 2017-06-01

Deskripsi

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 (p < 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