Prediction of Atherosclerosis Development by Modeling the Metabolism of Lipoproteins

Atherosclerosis is the disease related to coronary heart disease and stroke. The initiation of atherosclerosis is induced by physical stimuli which is shear stress on the endothelial cells and by endothelial activation. Development of atherosclerosis and foam cell formation is highly related to lipoprotein metabolism especially the concentration of oxidized low density lipoprotein(oxLDL). This essay presents an in-depth review of lipoprotein metabolism, including how chylomicron and chylomicron remnant works, how ApoB100 lipoprotein (VLDL, IDL and LDL) works, how high density lipoprotein(HDL) and reverse cholesterol transport works, and how these lipoproteins interact with each other. Moreover, other species and process which play the important role in lipoprotein metabolism such as lipoprotein lipase and beta-oxidation are reviewed. Then a model of lipoprotein metabolism based on plasma, liver, adipose and muscle compartment is presented. This model was used to analyze how the composition of dietary fat affects oxLDL concentration. Palm oil, olive oil and corn oil (enriched in saturated, monounsaturated and omega-6 fatty acids) were used as impacts. The result shows that corn oil has the largest amount of both double bond and oxidized double bond after meals which suggests that corn oil and other polyunsaturated fats are related to atherosclerosis

Acute glycogen synthase kinase-3 inhibition modulates human cardiac conduction

Glycogen synthase kinase 3 (GSK-3) inhibition has emerged as a potential therapeutic target for several diseases, including cancer. However, the role for GSK-3 regulation of human cardiac electrophysiology remains ill-defined. We demonstrate that SB216763, a GSK-3 inhibitor, can acutely reduce conduction velocity in human cardiac slices. Combined computational modeling and experimental approaches provided mechanistic insight into GSK-3 inhibition-mediated changes, revealing that decreased sodium-channel conductance and tissue conductivity may underlie the observed phenotypes. Our study demonstrates that GSK-3 inhibition in human myocardium alters electrophysiology and may predispose to an arrhythmogenic substrate; therefore, monitoring for adverse arrhythmogenic events could be considered

Chamber-specific transcriptional responses in atrial fibrillation

Atrial fibrillation (AF) is the most common cardiac arrhythmia, yet the molecular signature of the vulnerable atrial substrate is not well understood. Here, we delineated a distinct transcriptional signature in right versus left atrial cardiomyocytes (CMs) at baseline and identified chamber-specific gene expression changes in patients with a history of AF in the setting of end-stage heart failure (AF+HF) that are not present in heart failure alone (HF). We observed that human left atrial (LA) CMs exhibited Notch pathway activation and increased ploidy in AF+HF but not in HF alone. Transient activation of Notch signaling within adult CMs in a murine genetic model is sufficient to increase ploidy in both atrial chambers. Notch activation within LA CMs generated a transcriptomic fingerprint resembling AF, with dysregulation of transcription factor and ion channel genes, including Pitx2, Tbx5, Kcnh2, Kcnq1, and Kcnip2. Notch activation also produced distinct cellular electrophysiologic responses in LA versus right atrial CMs, prolonging the action potential duration (APD) without altering the upstroke velocity in the left atrium and reducing the maximal upstroke velocity without altering the APD in the right atrium. Our results support a shared human/murine model of increased Notch pathway activity predisposing to AF

Multifunctional sulfonium-based treatment for perovskite solar cells with less than 1% efficiency loss over 4,500-h operational stability tests

The stabilization of grain boundaries and surfaces of the perovskite layer is critical to extend the durability of perovskite solar cells. Here we introduced a sulfonium-based molecule, dimethylphenethylsulfonium iodide (DMPESI), for the post-deposition treatment of formamidinium lead iodide perovskite films. The treated films show improved stability upon light soaking and remains in the black α phase after two years ageing under ambient condition without encapsulation. The DMPESI-treated perovskite solar cells show less than 1% performance loss after more than 4,500 h at maximum power point tracking, yielding a theoretical T80 of over nine years under continuous 1-sun illumination. The solar cells also display less than 5% power conversion efficiency drops under various ageing conditions, including 100 thermal cycles between 25 °C and 85 °C and an 1,050-h damp heat test