Torzewski Michael, Ravandi Amir, Yeang Calvin, Edel Andrea, Bhindi Rahul, Kath Stefan, Twardowski Laura, Schmid Jens, Yang Xiaohong, Franke Ulrich F W, Witztum Joseph L, Tsimikas Sotirios
Department of Laboratory Medicine, Robert-Bosch-Hospital, Germany.
Cardiac Sciences Program, University of Manitoba and Institute of Cardiovascular Sciences, St. Boniface Hospital.
JACC Basic Transl Sci. 2017 Jun;2(3):229-240. doi: 10.1016/j.jacbts.2017.02.004. Epub 2017 Jun 26.
The 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 were categorized pathologically from Both ATX-apoB and ATX-apo(a) were measureable in plasma. Lp(a), autotaxin, OxPL and MDA epitopes progressively increased in immunostaining (p<0.001 for all). Six species of OxPL and LysoPA were identified following 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 etiological factor in CAVS.
该基因是钙化性主动脉瓣狭窄(CAVS)唯一的单基因风险因素。自分泌运动因子(ATX)从氧化磷脂(OxPL)生成的氧化磷脂和溶血磷脂酸具有促炎作用。主动脉瓣叶经病理分类。血浆中可检测到ATX-载脂蛋白B和ATX-载脂蛋白(a)。脂蛋白(a)、自分泌运动因子、氧化磷脂和丙二醛表位在免疫染色中逐渐增加(所有p<0.001)。从瓣膜小叶中提取后鉴定出六种氧化磷脂和溶血磷脂酸。CAVS患者血浆和主动脉瓣叶中存在一系列病理相关的、与脂蛋白(a)相关的分子,这表明脂蛋白(a)是CAVS的关键病因因素。