SPECT/CT imaging for tracking subendothelial retention of electronegative low-density lipoprotein in vivo.

Autor: Law SH; Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan., Ke CC; Department of Medical Imaging and Radiological Sciences, College of Health Sciences, Kaohsiung Medical University, Taiwan; Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan., Chu CS; Division of Cardiology, Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan; Division of Cardiology, Department of International Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Center for Lipid Biosciences, Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan., Liu SH; Faculty of Health Sciences, Bristol Medical School, Bristol, England, United Kingdom., Weng MC; Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan., Ke LY; Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Lipid Biosciences, Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Graduate Institute of Medicine & Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: kly@gap.kmu.edu.tw., Chan HC; Department of Medical Laboratory Science, College of Medicine, I-Shou University, Kaohsiung, Taiwan. Electronic address: huachen.chan@gmail.com.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2023 Oct 01; Vol. 250, pp. 126069. Date of Electronic Publication: 2023 Aug 02.
DOI: 10.1016/j.ijbiomac.2023.126069
Abstrakt: The fifth subfraction of low-density lipoprotein (L5 LDL) can be separated from human LDL using fast-protein liquid chromatography with an anion exchange column. L5 LDL induces vascular endothelial injury both in vitro and in vivo through the lectin-like oxidized LDL receptor-1 (LOX-1). However, no in vivo evidence shows the tendency of L5 LDL deposition on vascular endothelium and links to dysfunction. This study aimed to investigate L5 LDL retention in vivo using SPECT/CT imaging, with Iodine-131 ( 131 I)-labeled and injected into six-month-old apolipoprotein E knockout (apoE -/- ) mice through tail veins. Besides, we examined the biodistribution of L5 LDL in tissues and analyzed the intracellular trafficking in human aortic endothelial cells (HAoECs) by confocal microscopy. The impacts of L5 LDL on HAoECs were analyzed using electron microscopy for mitochondrial morphology and western blotting for signaling. Results showed 131 I-labeled-L5 was preferentially deposited in the heart and vessels compared to L1 LDL. Furthermore, L5 LDL was co-localized with the mitochondria and associated with mitofusin (MFN1/2) and optic atrophy protein 1 (OPA1) downregulation, leading to mitochondrial fission. In summary, L5 LDL exhibits a propensity for subendothelial retention, thereby promoting endothelial dysfunction and the formation of atherosclerotic lesions.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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