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.

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

Santonastaso, Alice
Investigation
;
Bolanos-Garcia, Victor M
Membro del Collaboration Group
;
Scotti, Claudia
Project Administration
2021

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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/1447815
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