Interfacial studies of four Lp(a) isoforms: relationship between stability and isoforms?

International audienceLipoprotein(a) [Lp(a)] was identified in 1963 in human serum as an LDL-like particle and is today recognized as an important risk factor for cardiovascular diseases (Ref: Nordestgaard and col. Lipoprotein(a) as a Cardiovascular Risk Factor: Current Status. Eur Heart J 2010; 31, 2844-53). The LDL-like core of Lp(a) is covalently bound to a unique plasminogen-related glycoprotein, called apolipoprotein(a) [apo(a)]. This protein is highly polymorphic between individuals due to a specific domain namely Kringle IV type2 (KIV-2), which can be present as tandemly repeated from 3 to >40 times. Apo(a) seems to be also responsible of many of the pro-atherogenic and pro-trombotic properties of Lp(a). For example, smaller apo(a) isoforms (i.e. Lp(a) isoforms with a low number of KIV-2 copies) correlate with higher cardiovascular risk (Ref: Gazzaruso C, et al. Association of lipoprotein(a) levels and apolipoprotein(a) phenotypes with coronary heart disease in patients with essential hypertension. J Hypertens 1997;15(3):227-35). However, the molecular basis underlying the different atherogenic potential has not been fully understood. Biophysical characterization of different Lp(a) isoforms may offer insights into the role of apo(a) size in atherosclerotic diseases. In this work, we present interfacial measurements of four purified Lp(a) isoforms containing 20, 24, 25 and 29 KIV-2 domains (K20, K24, K25, and K29)