Lipoprotein(a), a clinically elusive lipoprotein particle.

Abstract

The existence of lipoprotein(a) [Lp(a)] in human plasma was first reported by Berg1 in 1963 as an antigen associated with LDL. Berg and Mohr2 also found in family studies that the presence of Lp(a) was genetically determined by an autosomal mode of inheritance. Later studies provided evidence that Lp(a) is a specific class of lipoprotein particles with a lipid composition very similar to that of LDL. Lp(a) differs from LDL by the presence of a highly glycosylated protein of variable mass, termed apolipoprotein(a) [apo(a)], linked by a covalent bond to apolipoprotein (apo) B-100. The association between Lp(a) and coronary heart disease was first reported in the early 1970s,3 but what triggered a vast train of research on Lp(a) was the discovery in 1987 of the structural homology between apo(a) and plasminogen, a key protein of the coagulation cascade.4 Like plasminogen, apo(a) is composed of a kringle-containing domain and a serine protease domain. Apo(a) kringle domain is formed by one copy of plasminogen-like kringle 5 domain and multiple copies of the plasminogen-like kringle 4 (K4) domain. Ten basic K4 types,5 designated K4 type 1 through 10, are present in apo(a), all as a single copy, except K4 type 2, which is present in a variable number of copies ranging from 3 to >40.6 The varying number of K4 type 2 repeats is the major determinant of apo(a) size heterogeneity,7 giving origin to the large number of apo(a) isoforms detected in human plasma.8 In addition to apo(a) size heterogeneity, Lp(a) is heterogeneous in plasma levels, lysine-binding properties, and lipid, carbohydrate, and apolipoprotein composition, with apo E reported in 20% of plasma Lp(a) particles.9 …