Lipoprotein(a)

4018n/aENSG00000198670n/an/an/aNM_005577n/an/an/aLipoprotein(a) (also called Lp(a) or LPA) is a lipoprotein subclass. Genetic studies and numerous epidemiologic studies have identified Lp(a) as a risk factor for atherosclerotic diseases such as coronary heart disease and stroke.1i71: HIGH RESOLUTION CRYSTAL STRUCTURE OF APOLIPOPROTEIN(A) KRINGLE IV TYPE 7: INSIGHTS INTO LIGAND BINDING1jfn: SOLUTION STRUCTURE OF HUMAN APOLIPOPROTEIN(A) KRINGLE IV TYPE 61kiv: RECOMBINANT KRINGLE IV-10/M66 VARIANT OF HUMAN APOLIPOPROTEIN(A)2feb: NMR Solution Structure, Dynamics and Binding Properties of the Kringle IV Type 8 module of apolipoprotein(a)3kiv: RECOMBINANT KRINGLE IV-10/M66 VARIANT OF HUMAN APOLIPOPROTEIN(A)4kiv: RECOMBINANT KRINGLE IV-10/W72R MUTANT OF HUMAN APOLIPOPROTEIN(A) Lipoprotein(a) (also called Lp(a) or LPA) is a lipoprotein subclass. Genetic studies and numerous epidemiologic studies have identified Lp(a) as a risk factor for atherosclerotic diseases such as coronary heart disease and stroke. Lipoprotein(a) was discovered in 1963 by Kåre Berg. The human gene encoding apolipoprotein(a) was cloned in 1987. Lipoprotein(a) consists of an LDL-like particle and the specific apolipoprotein(a) , which is bound covalently to the apoB of the LDL-like particle. Lp(a) plasma concentrations are highly heritable and mainly controlled by the apolipoprotein(a) gene located on chromosome 6q26-27. Apo(a) proteins vary in size due to a size polymorphism , which is caused by a variable number of so-called kringle IV repeats in the LPA gene. This size variation at the gene level is expressed on the protein level as well, resulting in apo(a) proteins with 10 to > 50 kringle IV repeats (each of the variable kringle IV consists of 114 amino acids). These variable apo(a) sizes are known as 'apo(a) isoforms'. There is a general inverse correlation between the size of the apo(a) isoform and the Lp(a) plasma concentration. One theory for the size to plasma level correlation involves difference rates of protein synthesis. There appears to be a relationship between the number of kringle repeats and the processing time of the precursor apo(a) protein. That is, the larger the isoform, the more apo(a) precursor protein accumulates intracellularly in the endoplasmic reticulum. Lipoprotein(a) is not fully synthesized until the precursor protein is released from the cell, so the slower rate of production for the larger isoforms limits the plasma concentration. Apo(a) is expressed by liver cells (hepatocytes), and the assembly of apo(a) and LDL particles seems to take place at the outer hepatocyte surface. The half-life of Lp(a) in the circulation is approximately three to four days. The mechanism and sites of Lp(a) catabolism are largely unknown. Uptake via the LDL receptor is not a major pathway of Lp(a) metabolism. The kidney has been identified as playing a role in Lp(a) clearance from plasma.