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

J Cell Physiol. 2019 Jul;234(7):10512-10522. doi: 10.1002/jcp.27723. Epub 2018 Nov 27.

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.

Keywords: atrial fibrillation (AF); cholinergic activity; epicardial fat cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism*
  • Adipose Tissue / drug effects*
  • Adipose Tissue / metabolism
  • Adiposity / drug effects*
  • Aged
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / metabolism
  • Autonomic Nervous System / drug effects
  • Autonomic Nervous System / metabolism
  • Cholinergic Agents / pharmacology*
  • Female
  • Heart Atria / drug effects*
  • Heart Atria / metabolism
  • Humans
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Male
  • Receptors, Muscarinic / metabolism
  • Up-Regulation / drug effects

Substances

  • Cholinergic Agents
  • Receptors, Muscarinic
  • Acetylcholine