Low levels of transgenic mouse apolipoprotein E (apoE) suppress atherosclerosis in apoE knockout (apoE-/-) mice without normalizing plasma cholesterol. To test whether this is due to facilitation of cholesterol efflux from the vessel wall, we produced apoA-I-/-/apoE-/- mice with or without the transgene. Even without apoA-I and HDL, apoA-I-/-/apoE-/- mice had the same amount of aorta cholesteryl ester as apoE-/- mice. Low apoE in the apoA-I-/-/apoE-/- transgenic mice reduced aortic lesions by 70% versus their apoA-I-/-/apoE-/- siblings. To define the free cholesterol (FC) efflux capacity of lipoproteins from the various genotypes, sera were assayed on macrophages expressing ATP-binding cassette transporter A1 (ABCA1). Surprisingly, ABCA1 FC efflux was twice as high to sera from the apoA-I-/-/apoE-/- or apoE-/- mice compared with wild-type mice, and this activity correlated with serum apoA-IV. Immunodepletion of apoA-IV from apoA-I-/-/apoE-/- serum abolished ABCA1 FC efflux, indicating that apoAI-V serves as a potent acceptor for FC efflux via ABCA1. With increasing apoE expression, apoA-IV and FC acceptor capacity decreased, indicating a reciprocal relationship between plasma apoE and apoA-IV. Low plasma apoE (1-3 x 10(-8) M) suppresses atherosclerosis by as yet undefined mechanisms, not dependent on the presence of apoA-I or HDL or an increased capacity of serum acceptors for FC efflux.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1194/jlr.M300224-JLR200 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Alterations in LDL and HDL after an ischemic stroke associated with carotid atherosclerosis are reversed after 1 year.
J Lipid Res
December 2024
Cardiovascular Biochemistry Group, Institut de Recerca Sant Pau, (IR Sant Pau), Barcelona, Spain; CIBER of Diabetes and Metabolic Diseases (CIBERDEM), Spain. Electronic address:
Approximately 20% of ischemic strokes are attributed to the presence of atherosclerosis. Lipoproteins play a crucial role in the development of atherosclerosis, with LDL promoting atherogenesis and HDL inhibiting it. Therefore, both their concentrations and their biological properties are decisive factors in atherosclerotic processes.
View Article and Find Full Text PDFDifferent association of HDL-C, apoA-I, and HDL-C/apoA-I with multiple outcomes in HFrEF patients.
Int J Cardiol
December 2024
Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Medical Research Center, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou 510120, China; Nanhai Translational Innovation Center of Precision Immunology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Foshan 528200, China; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou 510120, China. Electronic address:
Background: High-density lipoprotein-cholesterol (HDL-C) has been considered a cardioprotective factor for several decades. However, its association with outcomes in patients with heart failure with reduced ejection fraction (HFrEF) remains controversial. We aimed to investigate the association of HDL-C, apolipoprotein A-I (apoA-I), and the HDL-C/apoA-I ratio with multiple outcomes of HFrEF patients and establish prognostic models using machine learning methods.
View Article and Find Full Text PDFBlood lipid metabolic biomarkers are emerging as significant prognostic indicators for survival in cancer patients.
BMC Cancer
December 2024
Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Background: Dyslipidemia is a common comorbidity in patients with cancer, yet the impact of abnormal lipid levels on tumor prognosis remains contentious. This study was conducted to synthesize the current evidence regarding the prognostic utility of blood lipid levels, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB), in predicting overall survival (OS) and disease-free survival (DFS) in cancer patients.
Methods: A comprehensive literature search was performed across electronic databases to assess the associations between blood lipid levels and OS or DFS in cancer patients.
Understanding lipidomics associations and the lipoprotein-related caveats in population epidemiology.
Am J Epidemiol
November 2024
Systems Epidemiology, Faculty of Medicine, University of Oulu, Oulu, Finland.
Mass spectrometry lipidomics is becoming customary to analyse serum/plasma samples in epidemiology. The measurables are molecular constituents of lipoprotein particles, but very little is known on the consequences of adjusting lipidomics data with lipoprotein measures. We studied two population cohorts with 5,657 and 2,036 participants.
View Article and Find Full Text PDFInhibiting IP6K1 confers atheroprotection by elevating circulating apolipoprotein A-I.
Metabolism
December 2024
Tianjin Key Laboratory of Metabolic Diseases, Department of Physiology and Pathophysiology, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, 22 Qixiangtai Road, Tianjin 300070, China; Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China. Electronic address:
Background And Aims: Atherosclerotic cardiovascular diseases are the leading cause of death. Apolipoprotein A-I (apoA-I) mediates cholesterol efflux to lower the risks of atherosclerosis. Elevating circulating apoA-I is an effective strategy for atheroprotection.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!