Remnant Clearance Capacity as a Determinant of Lipoprotein Oxidation: A Flux–capacity Framework
Abstract
The oxidative modification of apoB-containing lipoproteins has traditionally been considered to occur mainly after their retention within the arterial intima. However, oxidatively modified remnant-like lipoprotein particles are reproducibly detectable in the circulation under both fasting and postprandial conditions. This observation suggests that remnant oxidation may begin before arterial entry; however, the metabolic processes that permit such modifications still remain poorly understood. In this Review, we propose that delayed processing and the prolonged residence of triglyceride-rich lipoprotein (TRL) remnants provide temporal and spatial opportunities for oxidative modification in the circulation. TRLs are processed within an organized vascular-hepatic pathway involving GPIHBP1-bound lipoprotein lipase (LPL), progressive particle remodeling, apoE-dependent receptor recognition, and the hepatic uptake. We defined the integrated efficiency of this pathway as the remnant clearance capacity (RCC). Within the proposed Flux-Capacity framework, an imbalance between TRL production and RCC prolongs the remnant residence time and increases repeated exposure to endothelial surfaces, reactive oxygen species, inflammatory cells, and lipolysis-derived products. We further propose a two-stage model of remnant oxidation: limited oxidative modification may begin during prolonged circulation or endothelial processing, thus generating minimally modified remnants, whereas subsequent subendothelial retention permits more extensive oxidation and inflammatory amplification. This framework does not imply that the residence time directly demonstrates oxidation; rather,it identifies the residence time as a determinant of oxidative opportunity. Stable isotope kinetic studies, standardized meal testing, and molecular characterization of remnant-associated oxidative products are required to test this model. By linking impaired remnant clearance to pre-arterial oxidative modification, RCC provides a testable mechanistic framework for remnant-related residual cardiovascular risk.
Related
- Early metabolic remodeling of insulin sensitivity and substrate oxidation with lipoprotein changes at postoperative day 3 after sleeve gastrectomy
- Bypassing the Blood-Central Nervous System (CNS) Barrier: A Dual-Axis Framework for Amyotrophic Lateral Sclerosis (ALS) Utilizing Glymphatic-Lymphatic Clearance and In Situ Chaperone Synthesis.
- Developing a Conceptual Framework: Integrating Tumour, Macroenvironment and Resource (TMR) as a Composite Determinant of Ovarian Cancer Outcome in Diverse Resource Settings
- Rural-urban disparities and associated factors of SARS-CoV-2 infection in Zambia: A convergent mixed-methods study using the Proximate Determinant Framework.
- A literature-informed pharmacokinetic framework for polymyxin B dosing during continuous renal replacement therapy: integrating renal function and extracorporeal clearance
BibTeX
@article{nakajima2026remnant,
title = {{Remnant Clearance Capacity as a Determinant of Lipoprotein Oxidation: A Flux–capacity Framework}},
author = {Katsuyuki Nakajima and Masami Murakami and Akira Tanaka},
journal = {Journal of Atherosclerosis and Thrombosis},
year = {2026},
month = oct,
doi = {10.5551/jat.66284},
url = {https://www.jstage.jst.go.jp/article/jat/advpub/0/advpub_66284/_article},
note = {CC BY-NC-SA},
}
RIS
TY - JOUR
TI - Remnant Clearance Capacity as a Determinant of Lipoprotein Oxidation: A Flux–capacity Framework
AU - Katsuyuki Nakajima
AU - Masami Murakami
AU - Akira Tanaka
PY - 2026
DA - 2026/10/21
JO - Journal of Atherosclerosis and Thrombosis
DO - 10.5551/jat.66284
UR - https://www.jstage.jst.go.jp/article/jat/advpub/0/advpub_66284/_article
AB - The oxidative modification of apoB-containing lipoproteins has traditionally been considered to occur mainly after their retention within the arterial intima. However, oxidatively modified remnant-like lipoprotein particles are reproducibly detectable in the circulation under both fasting and postprandial conditions. This observation suggests that remnant oxidation may begin before arterial entry; however, the metabolic processes that permit such modifications still remain poorly understood. In this Review, we propose that delayed processing and the prolonged residence of triglyceride-rich lipoprotein (TRL) remnants provide temporal and spatial opportunities for oxidative modification in the circulation. TRLs are processed within an organized vascular-hepatic pathway involving GPIHBP1-bound lipoprotein lipase (LPL), progressive particle remodeling, apoE-dependent receptor recognition, and the hepatic uptake. We defined the integrated efficiency of this pathway as the remnant clearance capacity (RCC). Within the proposed Flux-Capacity framework, an imbalance between TRL production and RCC prolongs the remnant residence time and increases repeated exposure to endothelial surfaces, reactive oxygen species, inflammatory cells, and lipolysis-derived products. We further propose a two-stage model of remnant oxidation: limited oxidative modification may begin during prolonged circulation or endothelial processing, thus generating minimally modified remnants, whereas subsequent subendothelial retention permits more extensive oxidation and inflammatory amplification. This framework does not imply that the residence time directly demonstrates oxidation; rather,it identifies the residence time as a determinant of oxidative opportunity. Stable isotope kinetic studies, standardized meal testing, and molecular characterization of remnant-associated oxidative products are required to test this model. By linking impaired remnant clearance to pre-arterial oxidative modification, RCC provides a testable mechanistic framework for remnant-related residual cardiovascular risk.
SN - 1880-3873
SN - 1340-3478
ER -