👤 Alexander F A Keszei

Apolipoprotein E (ApoE) is a key regulator of lipid metabolism that binds to lipid nanoparticle (LNP) surfaces to mediate cellular interactions. However, the ApoE-LNP behavior is highly dependent on the LNP composition, and the underlying mechanisms remain unclear. Here, we show that subtle alterations in LNP surface lipids profoundly reshape the ApoE-LNP structure and intracellular trafficking. Using cryogenic electron microscopy and live-cell imaging, we demonstrate that replacing 10 mol % 1,2-distearoyl- Show less

Although triglycerides (TG) are a major risk factor for coronary artery disease (CAD), their exact role is still controversial. Recently, a T/C polymorphism in the promoter region of the apoA5 gene at position 1131 has been found that is associated with an increased plasma TG concentration. We investigated the role of this polymorphism in 308 Hungarian patients with CAD referred to coronary bypass surgery, and in 310 controls recruited from the same area. The prevalence of the apoA5-1131C allele was significantly higher among CAD patients than among controls (10.9% versus 5.7%; P < 0.001, Odds ratio (OR) = 1.99 (1.30-3.04)). Controls carrying the rare C allele had in average 23.0% (P < 0.001), subjects with CAD 13.8% (P < 0.001) higher TG levels compared to common allele homozygotes. The polymorphism was not associated with other conventional CAD risk factors or laboratory data of the patients. In logistic regression models adjusted for age, gender, presence of diabetes, BMI, smoking, LDL-C, HDL-C and hypertension a significantly increased risk of developing CAD was found in patients carrying the apoA5-1131C allele (P < 0.001; OR = 1.98 (1.14-3.48)), suggesting that this allele variant is an independent genetic risk factor for CAD. Show less