Lipoprotein(a)-60 Years Later-What Do We Know?

Abstract

Lipoprotein(a) (Lp(a)) molecule includes two protein components: apolipoprotein(a) and apoB100. The molecule is the main transporter of oxidized phospholipids (OxPL) in plasma. The concentration of this strongly atherogenic lipoprotein is predominantly regulated by the LPA gene expression. Lp(a) is regarded as a risk factor for several cardiovascular diseases. Numerous epidemiological, clinical and in vitro studies showed a strong association between increased Lp(a) and atherosclerotic cardiovascular disease (ASCVD), calcific aortic valve disease/aortic stenosis (CAVD/AS), stroke, heart failure or peripheral arterial disease (PAD). Although there are acknowledged contributions of Lp(a) to the mentioned diseases, clinicians struggle with many inconveniences such as a lack of well-established treatment lowering Lp(a), and common guidelines for diagnosing or assessing cardiovascular risk among both adult and pediatric patients. Lp(a) levels are different with regard to a particular race or ethnicity and might fluctuate during childhood. Furthermore, the lack of standardization of assays is an additional impediment. The review presents the recent knowledge on Lp(a) based on clinical and scientific research, but also highlights relevant aspects of future study directions that would approach more suitable and effective managing risk associated with increased Lp(a), as well as control the Lp(a) levels.

Keywords: PCSK9 inhibitor; antisense oligonucleotide; apolipoprotein (a); cardiovascular disease; coronary heart disease; lipoprotein (a).

Figure 1

The structure of lipoprotein(a). Lipoprotein(a) consists of two parts: LDL-like particle apolipoprotein B100 (apo-B100) and carried lipids and apolipoprotein(a) [apo(a)] covalently bound by disulfide bonds. Apo(a) is composed of repeating kringle IV (KIV): one copy of both KIV1 and KIV3-10 and variable KIV2 repetition. Additionally, apo(a) is composed of kringle V (KV) and an inactive protease-like domain (P).