Objective: Mutations in human apolipoprotein A-I (apoA-I) are associated with low high-density lipoprotein (HDL) cholesterol levels and pathological conditions such as premature atherosclerosis and amyloidosis. In this study we functionally characterized two natural human apoA-I mutations, L141RPisa and L159RFIN, in vivo.
Methods: We generated transgenic mice expressing either wild-type (WT) or the two mutant forms of human apoA-I on a mouse apoA-I(-/-) background and analyzed for abnormalities in their lipid and lipoprotein profiles. HDL structure and functionality, as well as atherosclerosis development following a 14-week high-fat diet were assessed in these mice.
Results: The expression of either apoA-I mutant was associated with markedly reduced serum apoA-I (<10% of WT apoA-I), total and HDL-cholesterol levels (∼20% and ∼7% of WT apoA-I, respectively) and the formation of few small size HDL particles with preβ2 and α3, α4 electrophoretic mobility. HDL particles containing either of the two apoA-I mutants exhibited attenuated anti-oxidative properties as indicated by their inability to prevent low-density lipoprotein oxidation, and by decreased activities of paraoxonase-1 and platelet-activating factor acetylhydrolase. However, the apoA-I(L141R)Pisa or apoA-I(L159R)FIN-containing HDL particles demonstrated increased capacity to promote ATP-Binding Cassette Transporter A1-mediated cholesterol efflux from macrophages. Expression of apoA-I(L141R)Pisa or apoA-I(L159R)FIN mutations in mice was associated with increased diet-induced atherosclerosis compared to either WT apoA-I transgenic or apoA-I(-/-) mice.
Conclusions: These findings suggest that natural apoA-I mutations L141RPisa and L159RFIN affect the biogenesis and the functionality of HDL in vivo and predispose to diet-induced atherosclerosis in the absence of any other genetic defect.
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http://dx.doi.org/10.1016/j.atherosclerosis.2015.08.028 | DOI Listing |
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.
Platelets
December 2024
Institute of Pharmacology and Toxicology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
Sci Rep
November 2024
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 56, Dongsu-ro, Bupyeong-gu, Incheon, 21431, Republic of Korea.
Previous studies suggest associations between the risk of developing chronic obstructive pulmonary disease (COPD) and adiponectin/leptin (ALR) and apolipoprotein B/A1 (APOR) ratios. This longitudinal observational study, using data from the Korean Genome and Epidemiology Study (KoGES), examined the rate of lung function decline, risk factors for the airflow obstruction (AFO), and the time to first AFO based on ALR and APOR groups. Among 5578 participants, high ALR and low APOR were associated with rapid decline in lung function and a shorter time to the first AFO.
View Article and Find Full Text PDFPLoS One
November 2024
Department of Experimental Medical Sciences, Unit of Medical Protein Science, Lund University, Lund, Sweden.
Apolipoprotein A-I (ApoA-I), the primary component of high-density lipoprotein (HDL) cholesterol primes β-cells to increase insulin secretion, however, the mechanisms involved are not fully defined. Here, we aimed to confirm ApoA-I receptors in β-cells and delineate ApoA-I-receptor pathways in β-cell insulin output. An LRC-TriCEPS experiment was performed using the INS-1E rat β-cell model and ApoA-I for unbiased identification of ApoA-I receptors.
View Article and Find Full Text PDFNanoscale Horiz
December 2024
New Cornerstone Science Laboratory, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Chinese Academy of Sciences (CAS), Beijing 100190, China.
Nanoparticle interactions with biological systems are intricate processes influenced by various factors, among which the formation of protein corona plays a pivotal role. This research investigates a novel aspect of nanoprotein corona-cell interactions, focusing on the impact of the protein corona on the recovery of disrupted tight junctions in endothelial cells. We demonstrate that the protein corona formed on the surface of star-shaped nanoparticles induces the aggregates of ZO-1, which is quite important for the barriers' integrity.
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