Activity

A total of 661 m6A peaks were significantly changed by MeRIP-seq. Gene Ontology (GO) analysis revealed that protein folding, ubiquitin-dependent ERAD pathway, and positive regulation of RNA polymerase II were the three most significantly altered biological processes in HFpEF. The pathways including proteasome, protein processing in the endoplasmic reticulum, and PI3K-Akt signaling pathway were significantly changed in HFpEF by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Conclusions The expression pattern of m6A regulators and m6A landscape is changed in HFpEF. This uncovers a new transcription-independent mechanism of translation regulation. Therefore, our data suggest that the modulation of epitranscriptomic processes, such as m6A methylation, might be an interesting target for therapeutic interventions.Cardiovascular diseases have been regarded as the leading cause of death around the world, with myocardial infarction (MI) being the most severe form. MI leads to myocardial apoptosis, cardiomyocyte fibrosis, and cardiomyocyte hypertrophy, ultimately leading to heart failure, and death. Micro RNAs (miRNAs) participate in the genesis and progression of myocardial pathology after MI by playing an important regulatory role. This review aims to summarize all available knowledge on the role of miRNAs in the myocardial pathological process after MI to uncover potential major target pathways. In addition, the main therapeutic methods and their latest progress are also reviewed. miRNAs can regulate the main signaling pathways as well as pathological processes. Thus, they have the potential to induce therapeutic effects. Hence, the combination of miRNAs with recently developed exosome nanocomplexes may represent the future direction of therapeutics.The physiologic activation of thermogenic brown and white adipose tissues (BAT/WAT) by cold exposure triggers heat production by adaptive thermogenesis, a process known to ameliorate hyperlipidemia and protect from atherosclerosis. Mechanistically, it has been shown that thermogenic activation increases lipoprotein lipase (LPL)-dependent hydrolysis of triglyceride-rich lipoproteins (TRL) and accelerates the generation of cholesterol-enriched remnants and high-density lipoprotein (HDL), which promotes cholesterol flux from the periphery to the liver. HDL is also subjected to hydrolysis by endothelial lipase (EL) (encoded by LIPG). Genome-wide association studies have identified various variants of EL that are associated with altered HDL cholesterol levels. However, a potential role of EL in BAT-mediated HDL metabolism has not been investigated so far. In the present study, we show that in mice, cold-stimulated activation of thermogenic adipocytes induced expression of Lipg in BAT and inguinal WAT but that loss of Lipg did not affect gene expression of thermogenic markers. Furthermore, in both wild type (WT) and Lipg-deficient mice, activation of thermogenesis resulted in a decline of HDL cholesterol levels. However, cold-induced remodeling of the HDL lipid composition was different between WT and Lipg-deficient mice. Notably, radioactive tracer studies with double-labeled HDL indicated that cold-induced hepatic HDL cholesterol clearance was lower in Lipg-deficient mice. Moreover, this reduced clearance was associated with impaired macrophage-to-feces cholesterol transport. Overall, these data indicate that EL is a determinant of HDL lipid composition, cholesterol flux, and HDL turnover in conditions of high thermogenic activity.Introduction Heart failure (HF) is a major cause of morbimortality both in men and women. Differences between sex in etiopathogenesis, response to treatment, and quality of care have been found in patients with HF. Females are usually under-represented in clinical trials and there is no solid evidence demonstrating the influence of sex in the prognostic of chronic HF. The primary objective of this study was to analyse the differences in mortality and probability of hospital readmission between males and females with HF. The secondary objective was to compare mortality and probability of hospital readmission by ejection fraction (reduced vs. preserved). Methods Patients with decompensated HF that were consecutively admitted to a Cardiology Service of a tertiary hospital for 4 years were recruited. De novo HF, death during hospitalization, programmed admissions and those patients with moderate left ventricular ejection fraction (LVEF) (40-50%) were discarded. Finally, 1,291 patients were included. Clinical prof although there was association between female sex and probability of readmission (OR = 1.37, IC 95% = 1.04-1.82, p = 0.02). Selleck RK-33 Conclusions Sex does not influence mid-term mortality in patients admitted for decompensated HF. Nevertheless, probability of readmission is higher in females independently from LVEF. Thus, it should be considered whether healthcare may be different depending on sex, and a more personalized and frequent care may be recommended in females.Cardiovascular diseases (CVDs) still represent the primary cause of mortality worldwide. Preclinical modeling by recapitulating human pathophysiology is fundamental to advance the comprehension of these diseases and propose effective strategies for their prevention, diagnosis, and treatment. In silico, in vivo, and in vitro models have been applied to dissect many cardiovascular pathologies. Computational and bioinformatic simulations allow developing algorithmic disease models considering all known variables and severity degrees of disease. In vivo studies based on small or large animals have a long tradition and largely contribute to the current treatment and management of CVDs. In vitro investigation with two-dimensional cell culture demonstrates its suitability to analyze the behavior of single, diseased cellular types. The introduction of induced pluripotent stem cell technology and the application of bioengineering principles raised the bar toward in vitro three-dimensional modeling by enabling the development of pathological tissue equivalents. This review article intends to describe the advantages and disadvantages of past and present modeling approaches applied to provide insights on some of the most relevant congenital and acquired CVDs, such as rhythm disturbances, bicuspid aortic valve, cardiac infections and autoimmunity, cardiovascular fibrosis, atherosclerosis, and calcific aortic valve stenosis.