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

Shi Hui Law; Chien-Chih Ke; Chih-Sheng Chu; Shu-Hsuan Liu; Mao-Chi Weng; Liang-Yin Ke; Hua-Chen Chan

doi:10.1016/j.ijbiomac.2023.126069

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

Int J Biol Macromol. 2023 Oct 1:250:126069. doi: 10.1016/j.ijbiomac.2023.126069. Epub 2023 Aug 2.

Authors

Shi Hui Law¹, Chien-Chih Ke², Chih-Sheng Chu³, Shu-Hsuan Liu⁴, Mao-Chi Weng⁵, Liang-Yin Ke⁶, Hua-Chen Chan⁷

Affiliations

¹ Department of Medical Laboratory Science and Biotechnology, College of Health Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan.
² 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.
³ 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.
⁴ Faculty of Health Sciences, Bristol Medical School, Bristol, England, United Kingdom.
⁵ Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan.
⁶ 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.
⁷ Department of Medical Laboratory Science, College of Medicine, I-Shou University, Kaohsiung, Taiwan. Electronic address: huachen.chan@gmail.com.

PMID: 37536403
DOI: 10.1016/j.ijbiomac.2023.126069

Abstract

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 (¹³¹I)-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 ¹³¹I-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.

Keywords: Detection of L5 LDL retention in vivo; Electronegative low-density lipoprotein (L5 LDL); Endothelial dysfunction; Formation of atherosclerotic lesions; Propensity for subendothelial retention.