title: Atrial fibrillation coincides with the advanced glycation end product N(ε)-(carboxymethyl)lysine in the atrium.
abstract: Presence of advanced glycation end products (AGEs) in the heart induces a proinflammatory phenotype. However, the presence of AGEs within atrial tissue of atrial fibrillation (AF) patients is unknown and was analyzed here. Left atrial appendage tissue from 33 AF patients and 9 controls was analyzed for the presence of the major AGEs N(ε)-(carboxymethyl)lysine (CML), VCAM-1, neutrophilic granulocytes, lymphocytes, and macrophages in both the fat tissue and myocardium separately. The total amount of fibrosis was also analyzed. Presence of CML was significantly higher in blood vessels of the left atrial appendage in AF patients as compared to controls, independent of diabetes mellitus. In AF patients, VCAM-1 expression in blood vessels and the numbers of infiltrated neutrophilic granulocytes, lymphocytes, and macrophages significantly increased compared to controls, and were highest in the fat tissue; there was no significant difference in fibrosis compared to controls. Interestingly, total amount of CML and fibrosis in AF and control patients correlated positively. Finally, there was no difference between AF patients based on AF type or surgical indication in the presence of CML, VCAM-1 expression, inflammatory cells, and fibrosis. Our results indicate that in AF the intramyocardial blood vessels of the left atrial appendage have an increased CML presence and proinflammatory status coinciding with a local increase in the number of inflammatory cells.
authors.affiliation: Department of Pathology, VU Medical Center, Amsterdam, The Netherlands; Department of Pathology, the Netherlands Forensic Institute, The Hague, The Netherlands; ICaR-VU, Amsterdam, The Netherlands. Electronic address: mpv.begieneman@vumc.nl.
authors.forename: Mark P V
authors.initials: MP
authors.lastname: Begieneman
authors.affiliation: Department of Pathology, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Liza
authors.initials: L
authors.lastname: Rijvers
authors.affiliation: Department of Pathology, the Netherlands Forensic Institute, The Hague, The Netherlands.
authors.forename: Bela
authors.initials: B
authors.lastname: Kubat
authors.affiliation: Department of Physiology, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Paulus
authors.affiliation: Department of Cardiothoracic Surgery, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Alexander B A
authors.initials: AB
authors.lastname: Vonk
authors.affiliation: Department of Cardiology, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Albert C
authors.initials: AC
authors.lastname: van Rossum
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.affiliation: Department of Cardiothorascic Surgery, Once Lieve Vrouwe Gasthius, Amsterdam, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Stooker
authors.affiliation: Department of Pathology, VU Medical Center, Amsterdam, The Netherlands; ICaR-VU, Amsterdam, The Netherlands; Department of Cardiothoracic Surgery, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Hans W M
authors.initials: HW
authors.lastname: Niessen
authors.affiliation: Department of Pathology, VU Medical Center, Amsterdam, The Netherlands; ICaR-VU, Amsterdam, The Netherlands.
authors.forename: Paul A J
authors.initials: PA
authors.lastname: Krijnen
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005355:Fibrosis; D006098:Granulocytes / Q000378:metabolism / Q000473:pathology; D006325:Heart Atria / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D008239:Lysine / Q000031:analogs & derivatives* / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D019010:Vascular Cell Adhesion Molecule-1; C048496:N(6)-carboxymethyllysine; D008239:Lysine