Calpains and cytokines in fibrillating human atria.
Atrial fibrillation (AF) is accompanied by intracellular calcium overload. The purpose of this study was to assess the role of calcium-dependent calpains and cytokines during AF. Atrial tissue samples from 32 patients [16 with chronic AF and 16 in sinus rhythm (SR)] undergoing open heart surgery were studied. Atrial expression of calpain I and II, calpastatin, troponin T (TnT), troponin C (TnC), and cytokines [interleukin (IL)-1 beta, IL-2, IL-6, IL-8, IL-10, transforming growth factor (TGF)-beta 1, and tumor necrosis factor-alpha] were determined. Expression of calpain I was increased during AF (461 +/- 201% vs. 100 +/- 34%, P < 0.05). Amounts of calpain II and calpastatin were unchanged. Total calpain enzymatic activity was more than doubled during AF (35.2 +/- 17.7 vs. 12.4 +/- 9.2 units, P < 0.05). In contrast to TnC, TnT levels were reduced in fibrillating atria by 26% (P < 0.05), corresponding to the myofilament disintegration seen by electron microscopy. Small amounts of only IL-2 and TGF-beta 1 mRNA and protein were detected regardless of the underlying cardiac rhythm. In conclusion, atria of patients with permanent AF show evidence of calpain I activation that might contribute to structural remodeling and contractile dysfunction, whereas there is no evidence of activation of tissue cytokines.
Goette
Andreas
A
Division of Cardiology, Department of Internal Medicine, University Hospital Magdeburg, 39120 Magdeburg, Germany. andreas.goette@medizin.uni-magdeburg.de
Arndt
Marco
M
Röcken
Christoph
C
Staack
Thorsten
T
Bechtloff
Roland
R
Reinhold
Dirk
D
Huth
Christof
C
Ansorge
Siegfried
S
Klein
Helmut U
HU
Lendeckel
Uwe
U
D008841:Actin Cytoskeleton / Q000473:pathology / Q000648:ultrastructure; D000328:Adult; D000368:Aged; D020517:Atrial Appendage / Q000503:physiopathology* / Q000648:ultrastructure; D001281:Atrial Fibrillation / Q000473:pathology / Q000503:physiopathology*; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D002154:Calpain / Q000096:biosynthesis* / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D053773:Transforming Growth Factor beta1
D002135:Calcium-Binding Proteins; D016207:Cytokines; D007376:Interleukin-2; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C033668:calpastatin; D002154:Calpain