👤 Adrian Chabowski

Atrial fibrillation (AF) has become the most common arrhythmia of clinical importance. A well-established and recommended therapeutic option for AF is the balloon-based cryoablation (CBA) method. There are still no sensitive biomarkers for AF prediction and cryoablation effectiveness assessment, therefore in our prospective study, we examined the plasma content of apolipoproteins (Apo) and sphingolipids, as well as the distribution of selected sphingolipids among lipoprotein fractions. The study included 33 patients with AF on admission and 24 h after cryoablation therapy, while 20 healthy volunteers were recruited to the control group. Plasma Apo concentrations were determined using a multiplex assay kit measuring fluorescence signal, whereas the high-performance liquid chromatography (HPLC) method was applied to assess the total plasma sphingolipid levels as well as their content in isolated lipoprotein fractions. Our results showed that cryoballoon ablation in AF patients markedly reduced the level of almost all Apo compared to the individuals from the control and Pre-CBA groups (Apo-A1: -25.9% and -20.0%, Apo-A2: -19.9% and -17.3%, Apo-B: -26.8% and -14.4%, Apo-C1: -20.3% and -13.4%, Apo-D: -15.9% and -22.2%, Apo-E: -18.3% and -14.3%, and Apo-J: -36.4% and -21.5%, p < 0.05, respectively). Importantly, the area under the curve of Apo-J (AUC 0.81; 95% CI, 0.71-0.92) indicates that it might be a useful biomarker of cryotherapy success in AF patients. Moreover, we also observed a pronounced increase in sphinganine (Sa; +33.5%), sphingosine (So; +24.6%), sphinganine-1-phosphate (Sa1P; +34.3%), and sphingosine-1-phosphate (So1P; +22.3%) concentrations in the Pre-CBA group in comparison with controls. This is the first study that evaluates such a broad panel of Apo and sphingolipids in patients with AF undergoing the CBA procedure, however, to confirm whether any of these parameters could be a clinically useful biomarker for predicting AF or assessing the effectiveness of treatment, further research will be necessary due to limitations of the study. Show less

The production of the omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from alpha-linolenic acid (ALA) relies on the delta-6 desaturase (D6D) enzyme encoded by the Fads2 gene. While EPA and DHA reduce hepatic triacylglycerol (TAG) storage and regulate lipogenesis, the independent impact of ALA is less understood. To address this gap in knowledge, hepatic fatty acid metabolism was investigated in male wild-type (WT) and Fads2 knockout (KO) mice fed diets (16% kcal from fat) containing either lard (no n-3 LCPUFA), flaxseed oil (ALA-rich), or menhaden oil (EPA/DHA rich) for 21 weeks. Fat content and composition, as well as markers of lipogenesis, glyceroneogenesis, and TAG synthesis, were analyzed using histology, gas chromatography, and reverse transcription quantitative PCR (RT-qPCR). Mice fed the menhaden diet had significantly lower hepatic TAG compared to both lard- and flax-fed mice, concomitant with changes in n-3 and n-6 LCPUFA in both TAG and phospholipid (PL) fractions (all P < 0.05). Flax-fed WT mice had lower liver TAG content compared to their KO counterparts. Menhaden-fed mice had significantly lower expression of key lipogenic (Scd1, Srebp-1c, Fasn, Fads1, and Fads2), glyceroneogenic (Pck1), and TAG synthesis (Agpat3) genes compared to lard, with flax-fed mice showing some intermediate effects. Gene expression effects were independent of D6D activity, since no differences were detected between WT and KO mice fed the same diet. This study demonstrates that EPA/DHA and not ALA itself is critical for the prevention of hepatic steatosis. Show less

Endothelial (EL) and lipoprotein (LPL) lipases are enzymes involved in lipoproteins metabolism and formation of atherosclerosis, a pathological feature of coronary artery disease (CAD). This paper examines the role of the lipases in the right atrial appendage (RAA) and coronary perivascular adipose tissue (PVAT) of patients with CAD alone or with accompanying diabetes. Additionally, correlation analysis for plasma concentration of the lipases, apolipoproteins (ApoA-ApoJ) and blood lipids (Chol, HDL-C, LDL-C, TAG) was performed. We observed that CAD had little effect on the lipases gene/protein levels in the RAA, while their transcript content was elevated in the PVAT of diabetic CAD patients. Interestingly, the RAA was characterized by higher expression of EL/LPL (EL: +1-fold for mRNA, +5-fold for protein; LPL: +2.8-fold for mRNA, +12-fold for protein) compared to PVAT. Furthermore, ApoA1 plasma concentration was decreased, whereas ApoC1 and ApoH were increased in the patients with CAD and/or diabetes. The concentrations of ApoC3 and ApoD were strongly positively correlated with TAG content in the blood, and the same was true for ApoB with respect to LDL-C and total cholesterol. Although plasma concentrations of EL/LPL were elevated in the patients with diabetes, CAD alone had little effect on blood, myocardial and perivascular fat expression of the lipases. Show less

Liver X receptors (LXRα and LXRβ) are ligand-activated transcription factors that regulate expression of genes involved in lipid and cholesterol metabolism. LXR expression has been identified in human and rodent cardiac tissue, however, its role in this tissue remains unclear. The aim of this study was to investigate effects of in vivo LXR activation on lipid metabolism in the rat myocardium under the conditions of low and high lipid intake. The experiments were performed on male Wistar rats fed for 5 weeks on either low fat diet (LFD) or high fat diet (HFD). Next, the animals were randomly divided into two groups receiving either LXR agonist - T0901317 (10mg/kg/d) or vehicle for the last week of the experiment. After anesthesia samples of the left ventricle and blood were taken. It was found that LXRβ is the dominant isoform in the rat myocardium and the expression of both LXR isoforms did not change after administration of T0901317. Agonist treatment induced hyperlipidemia in low fat fed rats and this effect was amplified in high fat fed rats. LXR agonist elevated content of myocardial triacylglycerols in animals fed on LFD and content of phospholipids in animals fed on HFD. Levels of the remaining examined lipid classes (nonesterified fatty acids, diacylglycerol, free cholesterol, cholesterol esters, ceramide) was decreased or unchaged after LXR activation. We conclude that administration of T0901317 does not lead to severe myocardial lipid accumulation in rats despite of its high plasma availability. Show less