Cholinergic activity regulates the secretome of epicardial adipose tissue: Association with atrial fibrillation

Abstract

Botulinum toxin injection on epicardial fat, which inhibits acetylcholine (ACh) release, reduced the presence of atrial fibrillation (AF) in patients after heart surgery. Thus, we wanted to study the profile of the released proteins of epicardial adipose tissue (EAT) under cholinergic activity (ACh treatment) and their value as AF predictors. Biopsies, explants, or primary cultures were obtained from the EAT of 85 patients that underwent open heart surgery. The quantification of muscarinic receptors (mAChR) by real‐time polymerase chain reaction or western blot showed their expression in EAT. Moreover, mAChR Type 3 was upregulated after adipogenesis induction (p < 0.05). Cholinergic fibers in EAT were detected by vesicular ACh transporter levels and/or acetylcholinesterase activity. ACh treatment modified the released proteins by EAT, which were identified by nano‐high‐performance liquid chromatography and TripleTOF analysis. These differentially released proteins were involved in cell structure, inflammation, or detoxification. After testing the plasma levels of alpha‐defensin 3 (inflammation‐involved protein) of patients who underwent open heart surgery ( n = 24), we observed differential levels between the patients who developed or did not develop postsurgery AF (1.58 ± 1.61 ng/ml vs. 6.2 ± 5.6 ng/ml; p < 0.005). The cholinergic activity on EAT might suggest a new mechanism for studying the interplay among EAT, autonomic nervous system dysfunction, and AF.

Inflammatory and lipid regulation by cholinergic activity in epicardial stromal cells from patients who underwent open‐heart surgery

“…[19][20][21] This study suggests the modulation of AF triggers embedded into epicardial fat as a new preventive strategy. However, cholinergic activity might also activate mechanisms on epicardial stromal cells through muscarinic receptors 23 with consequences on epicardial fat development and activity. We analysed the ACh effect on stromal F I G U R E 6 Differential expression of genes in patients regarding permanent atrial fibrillation (AF) and plasma levels regulation by cholinergic denervation.…”

Epicardial adipose tissue and atrial fibrillation: Possible mechanisms, potential therapies, and future directions

“…It could be drawn from abundant evidence of previous studies that AF and inflammation are closely associated . Many systemic inflammation biomarkers in serum are found to be upregulated in AF patients, such as C‐reactor protein, interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), interleukin‐10, interleukin‐1b (IL‐1b), tumor necrosis factor‐α (TNF‐α) .…”

Proteomic Analysis in Morquio A Cells Treated with Immobilized Enzymatic Replacement Therapy on Nanostructured Lipid Systems

“…Although 1D and 2D-PAGE are common proteomic approaches for high throughput screening of putative biomarkers in several disorders, particularly in animal studies [23,24], they have not been used in lysosomal diseases. On the other hand, mass spectrometry (MS) is a beneficial proteomic technology that allows proteomic pattern visualization and the identification of proteins [25,26] and their post-transcriptional modifications, such as phosphorylation, glycosylation, similar to 2D-Page approach [27]. In the last decade, MS has made significant progress by increasing the number of identified proteins [26].…”

“…On the other hand, mass spectrometry (MS) is a beneficial proteomic technology that allows proteomic pattern visualization and the identification of proteins [25,26] and their post-transcriptional modifications, such as phosphorylation, glycosylation, similar to 2D-Page approach [27]. In the last decade, MS has made significant progress by increasing the number of identified proteins [26]. Therefore, liquid chromatography (LC) coupled with MS is widely used for searching disease biomarkers [26] in samples such as biological fluids, tissues, cells, etc.…”

“…In the last decade, MS has made significant progress by increasing the number of identified proteins [26]. Therefore, liquid chromatography (LC) coupled with MS is widely used for searching disease biomarkers [26] in samples such as biological fluids, tissues, cells, etc. [28,29].…”