Lipoprotein(a) - Structure, Epidemiology, Function and Diagnostics of a Cardiovascular Risk Marker

Abstract

Decades after its first description by Berg 1963 lipoprotein(a) (Lp(a)) is an established risk marker of cardiovascular diseases which is independent from other risk markers. The main difference of Lp(a) compared to LDL is the apo(a) residue which is covalently bound to apoB. Apo(a) is a glycoprotein which underlies a large genetic polymorphism. The latter is caused by a variation of the kringle-IV-type-2 repeats of the protein which is characterized by a large structural homology to plasminogen. The Lp(a) plasma concentration in the population is highly skewed and determined to more than 90 % by genetic factors. In healthy subjects the Lp(a)-concentration is correlated to its synthesis and not to its metabolism. Plasma concentrations of Lp(a) are affected by different diseases (e.g. diseases of liver and kidney), hormonal factors (e.g. sexual steroids, glucocorticoids, thyroid hormones), individual and environmental factors (e.g. age, cigarette smoking) as well as pharmaceuticals (e.g. derivatives of nicotinic acid) and therapeutic procedures (lipid apheresis). However, even though a large number of studies on Lp(a) were performed up to now many details of its physiological function and regulation of plasma concentration are not yet understood. In addition, studies showed contradictory results because there were large differences of the included patients, use of not sufficiently validated tests as well as analysis of frozen samples. Aim of our review was to describe function and physiological regulation of Lp(a) as well as factors influencing its plasma concentration.

Lipoprotein(a) the Insurgent: A New Insight into the Structure, Function, Metabolism, Pathogenicity, and Medications Affecting Lipoprotein(a) Molecule

“…It was initially thought that LDL receptor (LDLR) in the liver is responsible for the degradation of Lp(a). However, there is evidence that LDLR has minimal or no effect on Lp(a) catabolism [20]. Many kinetic studies have reported that Lp(a) has a longer circulating time than does LDL-C due to the small affinity of Lp(a) for LDLR [17,20].…”

“…However, there is evidence that LDLR has minimal or no effect on Lp(a) catabolism [20]. Many kinetic studies have reported that Lp(a) has a longer circulating time than does LDL-C due to the small affinity of Lp(a) for LDLR [17,20]. is low affinity occurs because the apo(a) component interferes with the positioning of the LDLR [17].…”

“…Wound healing is achieved by multiple complex processes. Many investigators have reported the positive role of Lp(a) in wound healing [20,21,79]. Yano et al [79] measured the presence of Lp(a) in tissue during healing.…”

“…Similar to LDL, Lp(a) has a hydrophilic apo-B100 component located around a lipid core of cholesteryl esters (CEs) and triacylglycerols with many phospholipids and unesterified cholesterol at its surface [19]. According to Siekmeier et al [20], "corresponding to the physical resemblance to LDL, both lipoproteins are very indistinguishable to each other with respect to their structure" [21] (see Figure 1(b)). However, Lp(a) is distinguished from LDL-C by its hydrophilic highly glycosylated apo(a) portion (the PLG-like pathogenic component of Lp(a)) [17].…”

Fibrinogen, Lp(a), Microalbuminuria and Left Ventricular Mass Index: Cardiovascular Disease Risk factors in Diabetes

“…It has tendency to attract other Lp(a) particles, trap LDL, VLDL, blood infiltrates and calcium forming atheromatous plaque in response to vessel injury. Antifibrinolytic activity and adhesiveness makes it much more atherogenic than LDL [8].…”