Interfacial Activity of Lipoprotein (a) Isoforms with a Variable Number of Kringle IV Type 2 Repeats: A New Indicator of Cardiovascular Risk?

Ann Clin Lab Sci. 2021 Nov;51(6):795-804.

Abstract

Objective: Lipoprotein (a) [Lp(a)] is an LDL-like particle constituted by lipids, apolipoprotein B100 and apolipoprotein (a) [apo(a)], a multidomain glycoprotein whose molecular mass is dependent on the genetically encoded number of Kringle IV type 2 (KIV-2) repeats. Because Lp(a) isoforms have been associated with cardiovascular risk (CVR), we have investigated if their interfacial properties can contribute to distinguish between low and high-risk groups and thus be used as a new CVR indicator.

Methods: Four Lp(a) variants, each carrying a different apo(a) isoform (K20, K24, K25, and K29), were purified from plasma of homozygous donors and their interfacial properties characterized using ellipsometry and surface pressure techniques.

Results: Ellipsometry measurements revealed that these isoforms had a similar propensity to form adsorbed layers at hydrophobic-hydrophilic interfaces, but surface pressure enabled to clearly separate them into two groups: K20 and K24 on one side, and K25 and K29 on the other side.

Conclusion: Though K24 and K25 differ only by a single KIV-2 domain, their sharp difference in surface pressure suggests a critical threshold between the two Lp(a) forms, providing insights into the use of condensed matter approaches to monitor CVR. Our findings may represent a new laboratory window to assist medical decisions and to develop precision medicine treatments, practices, and products for CVR, which can be extended to other cardiovascular disease conditions.

Keywords: Lipoprotein (a); ellipsometry; precision medicine; surface pressure.

MeSH terms

  • Cardiovascular Diseases* / diagnosis
  • Cardiovascular Diseases* / metabolism
  • Cardiovascular Diseases* / therapy
  • Chemistry Techniques, Analytical / methods
  • Heart Disease Risk Factors
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Kringles / physiology
  • Lipid Metabolism
  • Lipoprotein(a)* / chemistry
  • Lipoprotein(a)* / metabolism
  • Precision Medicine / methods
  • Protein Isoforms* / chemistry
  • Protein Isoforms* / classification
  • Protein Isoforms* / isolation & purification
  • Surface Properties

Substances

  • Lipoprotein(a)
  • Protein Isoforms