Apolipoprotein E (APOE) is distributed across various human tissues and plays a crucial role in lipid metabolism. Recent investigations have uncovered an additional facet of APOE's functionality, revealing its role in host defense against bacterial infections. To assess the antibacterial attributes of APOE3 and APOE4, we conducted antibacterial assays using Pseudomonas aeruginosa and Escherichia coli. Exploring the interaction between APOE isoforms and lipopolysaccharides (LPSs) from E. coli, we conducted several experiments, including gel shift assays, CD, and fluorescence spectroscopy. Furthermore, the interaction between APOE isoforms and LPS was further substantiated through atomic resolution molecular dynamics simulations. The presence of LPS induced the aggregation of APOE isoforms, a phenomenon confirmed through specific amyloid staining, as well as fluorescence and electron microscopy. The scavenging effects of APOE3/4 isoforms were studied through both in vitro and in vivo experiments. In summary, our study established that APOE isoforms exhibit binding to LPS, with a more pronounced affinity and complex formation observed for APOE4 compared with APOE3. Furthermore, our data suggest that APOE isoforms neutralize LPS through aggregation, leading to a reduction of local inflammation in experimental animal models. In addition, both isoforms demonstrated inhibitory effects on the growth of P. aeruginosa and E. coli. These findings provide new insights into the multifunctionality of APOE in the human body, particularly its role in innate immunity during bacterial infections.

• Klíčová slova
• antimicrobial peptides, apolipoprotein E isoforms, endotoxin, host defense, protein aggregation,
• MeSH
• apolipoprotein E3 * metabolismus   chemie   farmakologie   MeSH
• apolipoprotein E4 * metabolismus   chemie   farmakologie   MeSH
• Escherichia coli metabolismus   MeSH
• lidé MeSH
• lipopolysacharidy * metabolismus   chemie   MeSH
• myši MeSH
• protein - isoformy chemie   metabolismus   MeSH
• Pseudomonas aeruginosa metabolismus   MeSH
• simulace molekulární dynamiky MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• apolipoprotein E3 * MeSH
• apolipoprotein E4 * MeSH
• lipopolysacharidy * MeSH
• protein - isoformy MeSH

Introduction: The cause of familial hypercholesterolemia (FH) is defect in LDL receptor or familial defect of apolipoprotein B-100 (FDB) or, rarely, defect in proprotein convertase subtilisin/kexin type 9. Identification and treatment of patients with FH improves their prognosis. Our data represent retrospective analysis of 50 years of specialised care in our center. Patients and Methods: A group of 1236 FH patients (841 women, 395 men; 993 study subjects and 243 relatives; mean age 44.8 ± 16.7 years) included 154 FDB patients followed at the Lipid Clinic of the General University Hospital in Prague since the mid-1960s to the present. Clinical diagnosis was based on the Dutch Lipid Clinic Network Criteria. Genetic analysis was performed using PCR-RFLP to detect FDB and apolipoprotein E (APOE) polymorphism. Biochemical data were collected and statistically analysed. Results: At baseline, mean LDL-C and total cholesterol (TC) levels of all FH patients combined were 6.49 ± 1.92 mmol/L and 8.95 ± 1.95 mmol/L, respectively. Their LDL-C levels decreased to 3.26 ± 1.57 mmol/L and TC levels to 5.43 ± 1.69 mmol/L during follow-up. In the subgroup of LDL receptor-mediated FH (non-FDB) patients, baseline LDL-C and TC levels of 6.61 ± 1.95 mmol/L and 9.09 ± 1.97 mmol/L declined to 3.21 ± 1.60 mmol/L and 5.39 ± 1.72 mmol/L, respectively, during follow-up. In the FDB subgroup of patients, baseline levels of LDL-C and TC were 5.57 ± 1.46 mmol/L and 7.88 ± 1.58 mmol/L decreasing to 3.45 ± 0.24 mmol/L and 5.58 ± 1.37 mmol/L, respectively, during follow-up. Differences were also found in the effects of various APOE isoforms on lipid lowering. A significant decrease in lipid parameters was observed with the E2E2 isoform whereas a minimal decrease was seen with the E4E4 and E3E3 isoforms. Conclusion: Whereas, overall, non-FDB patients had higher baseline lipid levels, these levels declined more appreciably compared with FDB patients during follow-up. Our retrospective analysis also found different effects of APOE isoforms on the decrease in lipid levels.

• Klíčová slova
• ASCVD, ApoB, ApoE isoform, LDL-C, Lp(a), familial defective apolipoprotein B-100, familial hypercholesterolemia, statin,
• Publikační typ
• časopisecké články MeSH