Proteomic and Kinetic Analyses Reveal Discordant Apolipoprotein Turnover and Support a Revised Model of Human Lipoprotein(a) Metabolism
Objective: Lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular disease composed of apolipoprotein(a) [APO(a)] covalently linked to apolipoprotein B100 (APOB). Although plasma Lp(a) concentrations are largely genetically determined, the mechanisms governing Lp(a) metabolism after particle assembly remain poorly understood. We sought to define the Lp(a) proteome and…
Lipoprotein(a) (Lp(a)), a risk factor for cardiovascular disease, is composed of apolipoprotein(a) (APO(a)) linked to apolipoprotein B100 (APOB). Researchers aimed to understand the metabolism of Lp(a) particles after assembly. To do this, they used stable isotope tracer studies and high-resolution techniques to analyze the Lp(a) proteome, kinetics, and extracellular vesicles (EVs).
In their findings, 92 proteins associated with Lp(a) were identified, mainly linked to immunity, coagulation, and atherogenesis. The APO(a)-APOB complex showed a slower clearance rate of 0.04 pools/day compared to APOB alone, which cleared at a rate of 0.25 pools/day. This difference was consistent regardless of plasma Lp(a) levels or APO(a) isoform size.
Interestingly, both APO(a) and APOB were found on circulating EVs, indicating that these vesicles might play a role in the remodeling of Lp(a) particles after they are secreted. The study challenges the idea that APO(a) and APOB behave as a single unit post-Lp(a) assembly, proposing a revised model of human Lp(a) metabolism.
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